PGA基聚电解质的静电络合、层层自组装及药物载体构建
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摘要
带相反电荷的聚电解质尤其是弱聚电解质间的作用力在很大程度上会受到pH值、离子强度和温度等因素的影响,因此利用聚电解质间的静电作用制备出的药物载体一般具有环境敏感性、可控性等诸多优点。药物载体用生物可降解聚电解质大多是天然高分子,如海藻酸钠、壳聚糖(CS)和明胶等。而天然高分子种类少,分子量不可控,机械强度差、降解速度快等[1-3],无法满足作为药物载体的应用需要。与天然高分子相比,生物可降解合成高分子作为药物载体具有分子量和结构可调控等优点。本课题以生物可降解合成聚电解质聚谷氨酸(PGA)和聚乙二醇单甲醚-聚谷氨酸嵌段共聚物(mPEGGA)为主要组分,选用两种聚电解质体系PGA/CS与mPEGGA/CS,深入研究不同因素对mPEGGA与CS络合行为的影响,同时探讨了层层自组装制备弱聚电解质多层膜的增长机理及不同因素对多层膜生长的影响,为构建药物载体奠定理论基础。通过层层自组装技术制备新型载药微球。
成功合成嵌段共聚物mPEGGA。将mPEG的端羟基改性为活性端氨基:第一步是对甲苯磺酰氯与mPEG进行酯化反应在端位上形成磺酸酯基;第二步是用邻苯二甲酰亚胺基团取代mPEG端位上的对甲苯磺酸酯基;最后一步则是利用水合肼脱去邻苯二甲酰亚胺基团,制得端氨基聚乙二醇单甲醚(mPEG-NH_2)。
利用mPEG-NH_2引发γ-苄基-L-谷氨酸-N-羧酸酐(NCA)开环聚合,成功合成聚乙二醇单甲醚-聚谷氨酸苄酯嵌段共聚物(mPEGBG)。在HBr作用下,成功脱去共聚物中苄基保护基团,制得嵌段共聚物mPEGGA。改变引发剂和单体摩尔比,合成两种分子量的共聚物。
详细研究了不同因素对mPEGGA与CS络合行为的影响,重点考察了共聚物中非离子亲水链段mPEG对聚电解质络合物(Polyelectrolyte complexes, PEC)结构性质的影响:通过溶液滴定法制备mPEGGA/CS聚电解质络合物。由于聚阴阳离子的链段长度差别大,同时共聚物中mPEG链段与CS可形成氢键,因此聚电解质络合物胶束(Polyion complex micelle)只能在非等化学配比条件下形成。粒度分析结果显示胶束直径在200nm左右,大大超过其它聚电解质络合物胶束以及PGA/CS胶束[4]的粒径。胶束的粒径随着mPEGGA分子量的增大而增大。透射电镜(TEM)显示胶束典型的核壳结构。在本体PEC (polyelectrolyte complexes in the solid state)中,mPEGGA与CS间存在较强的静电作用力,与聚电解质体系PGA/CS比较[4],共聚物中亲水链段mPEG削弱了两者的静电力。mPEG链段与CS间存在较强的氢键作用力,从而破坏了嵌段共聚物中原有的结晶结构。
探讨了弱聚电解质多层膜的生长机理及不同因素对多层膜增长的影响。利用交替沉积技术在二维模板表面构筑多层膜PGA/CS和mPEGGA/CS。构建PGA/CS多层膜的主要驱动力是静电力。PGA/CS多层膜按照先指数后直线形式生长。pH值增大,多层膜增长速率降低。离子强度增加,一定程度上屏蔽了聚电解质的有效电荷,从而使聚电解质更趋向采取卷曲构象,使膜增长速率加快。聚电解质溶液浓度增加,提供了更多有效的聚电解质链,导致多层膜的增长速率加快。与PGA/CS体系相比,mPEGGA/CS多层膜增长速度较快,这是由于共聚物中柔性的链段mPEG所致,另外一种原因可能与共聚物中mPEG链段与CS形成的氢键作用有关。共聚物mPEGGA分子量越大,聚离子链段长度越长,多层膜增长速度也越快。
首次提出以CS微球为模板采用层层自组装技术构建载药微球。以5-氟尿嘧啶为模型药物,乳化交联法制备表面带正电荷的CS载药微球,并以PGA和mPEGGA为聚阴离子,CS为聚阳离子在其表面层层组装。结果发现,交联剂浓度越大,CS微球表面电荷越小。模板电荷的改变并不对其表面聚电解质层的电位产生影响。共聚物分子量越大,聚离子链段越长,聚电解质电荷密度也越大,相应层的电位也就越高。对于mPEGGA/CS组装体系,静电力和氢键同时成为自组装的驱动力。以PGA/CS为内层,mPEGGA为最外层的载药微球有效地抑制了药物载体中常有的突释现象,与CS载药微球和载药微胶囊相比都显著地延长了药物的释放时间。
Drug carriers driven by electrostatic force always possess pH, temperature-stimulative ability. Much related work has been devoted to natural polymers, like CS, alginate,glutin and so on. However, some disadvantages of natural polymers limit their broad application in controlled release. In the work, two polyelectrolyte systems PGA/CS and mPEGGA/CS were used to fabricate novel drug-loaded microspheres. Effect of different factors on polyelectrolyte complexation between neutral-block-polyanion and polycation in dilute solution and solid state were scrutinized. We also investigated alternate depostion of PGA (or mPEGGA) and CS on 2D template and the influence of different factors on layer-by-layer. Based on the theory on polyelectrolyte complexation and alternate deposition, novel drug carrier was fabricated.
Amino-monomethoxypoly (ethylene glycol) (mPEG-NH_2) was synthesized by converting terminal hydroxyl groups of mPEG to primary amino groups. Monomethoxypoly (ethylene glycol) tosyalte (mPEG-oTs) was prepared at first, and then reaction with salt of phthalimide and finally hydrazinolysis. N-carboxy anhydride ofγ-benzyl-L-glutamate (NCA) was synthesized fromγ-benzyl-L-glutamate and triphosegen. Methoxy poly(ethylene glycol)-b-poly(γ-benzyl-L-glutamate) (mPEGBG) diblock copolymer was obtained by ring-opening polymerization NCA of using amino-terminated methoxy polyethylene glycol (mPEG) as macroinitiator. Theγ-benzyl protection groups were removed in the presence of HBr and the resultant polymer monomethoxy poly(ethylene glycol)-b-poly(γ-benzyl-L-glutamate) (mPEGGA) was obtained.
Polyelectrolyte complexation between mPEGGA as neutral-block-polyanion and chitosan (CS) as polycation has been scrutinized in aqueous solution as well as in the solid state. Water-soluble polyelectrolyte complexes (PEC) can be formed only under nonstoichiometric condition while phase separation is observed when approaching 1:1 molar mixing ratio in spite of the existence of hydrophilic mPEG block. This is likely due to mismatch in chain length between polyanion block of the copolymer and the polycation or hydrogen bonding between the components. Hydrodynamic size of primary or soluble PEC is determined to be about 200nm, which is larger than those reported in some literature. The increase in polyion chain length of the copolymer leads to the increase in the hydrodynamic size of the water-soluble PEC. Formation of spherical micelles by the mPEGGA/CS complex at nonstoichiometirc condition has been confirmed by the scanning electron microscopy observation (SEM) and transmission electron microscopy (TEM) observations. The homopolymer CS experiences attractive interaction with both mPEGA and PGA blocks within the copolymer. Competition of hydrogen bonding and electrostatic force in the system or hydrophilic mPEG segments weakens the electrostatic interaction between the oppositely charged polyions. The existence of hydrogen bonding restrains the mobility of mPEG chains of the copolymer and completely prohibits crystallization of mPEG segments.
Multilayer films based on PGA and CS were fabricated by Layer-by-Layer Assembly technique. The growths of CS and PGA deposition are both exponential to the deposition steps at first,although at different steep growth. We further studied the factors of the growth by UV-vis spectroscopy. QCM measurements combined with UV-vis spectra revealed the increase of the multilayer film growth at different pHs: pH=4.4>pH=5.0>pH=5.5. When at pH=6.5, the build-up of the multilayer stoped after the deposition of a few layers. Meanwhile, the (PGA/CS) multilayer film grows more rapidly with increasing concentration of the polyelectrolytes’solutions and ionic strength. The multilayer films of mPEGGA/CS grew exponentially as the function of the deposition steps. The molecular weight of the block copolymer could significantly influence the growth of films. The film of mPEGGA/CS with high molecular weight of PGA segment grows faster than that of low molecular weight.
We described an approach to fabricate microspheres by a combination of emulsion-crosslinking method and LbL assembly technique. Firstly, bare CS microspheres were obtained by a typical emulsion-crosslinking method. The multilayer microspheres were fabricated by a template-assisted assembly in a LbL manner, using poly(α, L-glutamic acid) and its copolymer methoxy poly(ethylene glycol)-b-Poly(α, L-glutamic acid) as polyanion and CS as polycation. The results determined byξ-potential measurement show thatξ-potential at the same layer does not depend on the surface charge of the template. For polyelectrolytes of a lower charge density, lower values ofξ-potential can be obtained. The system is believed to be effective to entrap hydrophilic ionic drug as shown in the paper. Using 5-Fu as model drug, controlled release behaviour of novel drug-loaded microspheres using (PGA/CS)4 as inner layers and mPEGGA as outmost layer were investigated. It is found that the release rate is slower than that of typical CS microspheres and microcapusles.
成功合成嵌段共聚物mPEGGA。将mPEG的端羟基改性为活性端氨基:第一步是对甲苯磺酰氯与mPEG进行酯化反应在端位上形成磺酸酯基;第二步是用邻苯二甲酰亚胺基团取代mPEG端位上的对甲苯磺酸酯基;最后一步则是利用水合肼脱去邻苯二甲酰亚胺基团,制得端氨基聚乙二醇单甲醚(mPEG-NH_2)。
利用mPEG-NH_2引发γ-苄基-L-谷氨酸-N-羧酸酐(NCA)开环聚合,成功合成聚乙二醇单甲醚-聚谷氨酸苄酯嵌段共聚物(mPEGBG)。在HBr作用下,成功脱去共聚物中苄基保护基团,制得嵌段共聚物mPEGGA。改变引发剂和单体摩尔比,合成两种分子量的共聚物。
详细研究了不同因素对mPEGGA与CS络合行为的影响,重点考察了共聚物中非离子亲水链段mPEG对聚电解质络合物(Polyelectrolyte complexes, PEC)结构性质的影响:通过溶液滴定法制备mPEGGA/CS聚电解质络合物。由于聚阴阳离子的链段长度差别大,同时共聚物中mPEG链段与CS可形成氢键,因此聚电解质络合物胶束(Polyion complex micelle)只能在非等化学配比条件下形成。粒度分析结果显示胶束直径在200nm左右,大大超过其它聚电解质络合物胶束以及PGA/CS胶束[4]的粒径。胶束的粒径随着mPEGGA分子量的增大而增大。透射电镜(TEM)显示胶束典型的核壳结构。在本体PEC (polyelectrolyte complexes in the solid state)中,mPEGGA与CS间存在较强的静电作用力,与聚电解质体系PGA/CS比较[4],共聚物中亲水链段mPEG削弱了两者的静电力。mPEG链段与CS间存在较强的氢键作用力,从而破坏了嵌段共聚物中原有的结晶结构。
探讨了弱聚电解质多层膜的生长机理及不同因素对多层膜增长的影响。利用交替沉积技术在二维模板表面构筑多层膜PGA/CS和mPEGGA/CS。构建PGA/CS多层膜的主要驱动力是静电力。PGA/CS多层膜按照先指数后直线形式生长。pH值增大,多层膜增长速率降低。离子强度增加,一定程度上屏蔽了聚电解质的有效电荷,从而使聚电解质更趋向采取卷曲构象,使膜增长速率加快。聚电解质溶液浓度增加,提供了更多有效的聚电解质链,导致多层膜的增长速率加快。与PGA/CS体系相比,mPEGGA/CS多层膜增长速度较快,这是由于共聚物中柔性的链段mPEG所致,另外一种原因可能与共聚物中mPEG链段与CS形成的氢键作用有关。共聚物mPEGGA分子量越大,聚离子链段长度越长,多层膜增长速度也越快。
首次提出以CS微球为模板采用层层自组装技术构建载药微球。以5-氟尿嘧啶为模型药物,乳化交联法制备表面带正电荷的CS载药微球,并以PGA和mPEGGA为聚阴离子,CS为聚阳离子在其表面层层组装。结果发现,交联剂浓度越大,CS微球表面电荷越小。模板电荷的改变并不对其表面聚电解质层的电位产生影响。共聚物分子量越大,聚离子链段越长,聚电解质电荷密度也越大,相应层的电位也就越高。对于mPEGGA/CS组装体系,静电力和氢键同时成为自组装的驱动力。以PGA/CS为内层,mPEGGA为最外层的载药微球有效地抑制了药物载体中常有的突释现象,与CS载药微球和载药微胶囊相比都显著地延长了药物的释放时间。
Drug carriers driven by electrostatic force always possess pH, temperature-stimulative ability. Much related work has been devoted to natural polymers, like CS, alginate,glutin and so on. However, some disadvantages of natural polymers limit their broad application in controlled release. In the work, two polyelectrolyte systems PGA/CS and mPEGGA/CS were used to fabricate novel drug-loaded microspheres. Effect of different factors on polyelectrolyte complexation between neutral-block-polyanion and polycation in dilute solution and solid state were scrutinized. We also investigated alternate depostion of PGA (or mPEGGA) and CS on 2D template and the influence of different factors on layer-by-layer. Based on the theory on polyelectrolyte complexation and alternate deposition, novel drug carrier was fabricated.
Amino-monomethoxypoly (ethylene glycol) (mPEG-NH_2) was synthesized by converting terminal hydroxyl groups of mPEG to primary amino groups. Monomethoxypoly (ethylene glycol) tosyalte (mPEG-oTs) was prepared at first, and then reaction with salt of phthalimide and finally hydrazinolysis. N-carboxy anhydride ofγ-benzyl-L-glutamate (NCA) was synthesized fromγ-benzyl-L-glutamate and triphosegen. Methoxy poly(ethylene glycol)-b-poly(γ-benzyl-L-glutamate) (mPEGBG) diblock copolymer was obtained by ring-opening polymerization NCA of using amino-terminated methoxy polyethylene glycol (mPEG) as macroinitiator. Theγ-benzyl protection groups were removed in the presence of HBr and the resultant polymer monomethoxy poly(ethylene glycol)-b-poly(γ-benzyl-L-glutamate) (mPEGGA) was obtained.
Polyelectrolyte complexation between mPEGGA as neutral-block-polyanion and chitosan (CS) as polycation has been scrutinized in aqueous solution as well as in the solid state. Water-soluble polyelectrolyte complexes (PEC) can be formed only under nonstoichiometric condition while phase separation is observed when approaching 1:1 molar mixing ratio in spite of the existence of hydrophilic mPEG block. This is likely due to mismatch in chain length between polyanion block of the copolymer and the polycation or hydrogen bonding between the components. Hydrodynamic size of primary or soluble PEC is determined to be about 200nm, which is larger than those reported in some literature. The increase in polyion chain length of the copolymer leads to the increase in the hydrodynamic size of the water-soluble PEC. Formation of spherical micelles by the mPEGGA/CS complex at nonstoichiometirc condition has been confirmed by the scanning electron microscopy observation (SEM) and transmission electron microscopy (TEM) observations. The homopolymer CS experiences attractive interaction with both mPEGA and PGA blocks within the copolymer. Competition of hydrogen bonding and electrostatic force in the system or hydrophilic mPEG segments weakens the electrostatic interaction between the oppositely charged polyions. The existence of hydrogen bonding restrains the mobility of mPEG chains of the copolymer and completely prohibits crystallization of mPEG segments.
Multilayer films based on PGA and CS were fabricated by Layer-by-Layer Assembly technique. The growths of CS and PGA deposition are both exponential to the deposition steps at first,although at different steep growth. We further studied the factors of the growth by UV-vis spectroscopy. QCM measurements combined with UV-vis spectra revealed the increase of the multilayer film growth at different pHs: pH=4.4>pH=5.0>pH=5.5. When at pH=6.5, the build-up of the multilayer stoped after the deposition of a few layers. Meanwhile, the (PGA/CS) multilayer film grows more rapidly with increasing concentration of the polyelectrolytes’solutions and ionic strength. The multilayer films of mPEGGA/CS grew exponentially as the function of the deposition steps. The molecular weight of the block copolymer could significantly influence the growth of films. The film of mPEGGA/CS with high molecular weight of PGA segment grows faster than that of low molecular weight.
We described an approach to fabricate microspheres by a combination of emulsion-crosslinking method and LbL assembly technique. Firstly, bare CS microspheres were obtained by a typical emulsion-crosslinking method. The multilayer microspheres were fabricated by a template-assisted assembly in a LbL manner, using poly(α, L-glutamic acid) and its copolymer methoxy poly(ethylene glycol)-b-Poly(α, L-glutamic acid) as polyanion and CS as polycation. The results determined byξ-potential measurement show thatξ-potential at the same layer does not depend on the surface charge of the template. For polyelectrolytes of a lower charge density, lower values ofξ-potential can be obtained. The system is believed to be effective to entrap hydrophilic ionic drug as shown in the paper. Using 5-Fu as model drug, controlled release behaviour of novel drug-loaded microspheres using (PGA/CS)4 as inner layers and mPEGGA as outmost layer were investigated. It is found that the release rate is slower than that of typical CS microspheres and microcapusles.
引文
[1] Martina M, Hutmacher D W. Biodegradable polymers applied in tissue engineering research: A review[J]. Polymer International, 2007, 56(2): 145～157.
[2] Pasut G, Veronese F M. Polymer-drug conjugation, recent achievements and general strategies[J]. Progress in Polymer Science, 2007, 32(8-9): 933～961.
[3] Nishiyama N, Kataoka K. Current state, achievements, and future prospects of polymeric micelles as nanocarriers for drug and gene delivery[J]. Pharmacology & Therapeutics, 2006, 112(3): 630～648.
[4] Dai Z, Yin J, Yan S, et al. Polyelectrolyte complexes based on chitosan and poly(α,L-glutamic acid)[J]. Polymer International, 2007, 56(9): 1122～1127.
[5] Krol S, Del G S, Grupillo M, et al. Multilayer nanoencapsulation. new approach for immune protection of human pancreatic islets[J]. Nano Letters, 2006, 6(9): 1933～1939.
[6] Jewell C M, Zhang J, Fredin N J, et al. Release of plasmid DNA from intravascular stents coated with ultrathin multilayered polyelectrolyte films[J]. Biomacromolecules, 2006, 7(9): 2483～2491.
[7] Philipp B, Dautzenberg H, Linow K J, et al. Polyelectrolyte complexes. Recent developments and open problems[J]. Progress in Polymer Science (Oxford), 1989, 14(1): 91～172.
[8] Th A F, M M, Dautzenberg H, et al. Polyelectrolyte Complexes[J]. Advances in Polymer Science, 2004, 166(1): 113～171.
[9] Tsuchida E, Abe K, Honma M. Aggregation of Polyion Complexes between Synthetic Polyelectrolytes[J]. Macromolecules, 1976, 9(1): 112～117.
[10] Nikolaeva O, Budtova T, Alexeev V, et al. Interpolymer complexation between polyacrylic acid and cellulose ethers: Formation and properties[J]. Journal of Polymer Science, Part B: Polymer Physics, 2000, 38(10): 1323～1330.
[11] Mekhloufi G, Sanchez C, Renard D, et al. PH-induced structural transitions during complexation and coacervation of β-lactoglobulin and acacia gum[J].Langmuir, 2005, 21(1): 386～394.
[12] Dautzenberg H. Polyelectrolyte Complex Formation in Highly Aggregating Systems. 1. Effect of Salt: Polyelectrolyte Complex Formation in the Presence of NaCl[J]. Macromolecules, 1997, 30(25): 7810～7815.
[13] Karibyants N, Dautzenberg H, Coelfen H. Characterization of PSS/PDADMAC-co-AA polyelectrolyte complexes and their stoichiometry using analytical ultracentrifugation[J]. Macromolecules, 1997, 30(25): 7803～7809.
[14] Karibyants N, Dautzenberg H. Preferential binding with regard to chain length and chemical structure in the reactions of formation of quasi-soluble polyelectrolyte complexes[J]. Langmuir, 1998, 14(16): 4427～4434.
[15] Schatz C, Lucas J -, Viton C, et al. Formation and properties of positively charged colloids based on polyelectrolyte complexes of biopolymers[J]. Langmuir, 2004, 20(18): 7766～7778.
[16] Starodubtsev S G, Dembo A T, Dembo K A. Effect of Polymer Charge Density and Ionic Strength on the Formation of Complexes between Sodium Arylamido-2-methyl-1-propane-sulfonate-co-acrylamide Gels and Cetylpyridinium Chloride[J]. Langmuir, 2004, 20(16): 6599～6604.
[17] Hugerth A, Caram-Lelham N, Sundelof L O. The Effect of charge density and conformation on the polyelectrolyte complex formation between carrageenan and chitosan[J]. Carbohydrate Polymers, 1997, 34(3): 149～156.
[18] Buchhammer H M, Mende M, Oelmann M. Formation of mono-sized polyelectrolyte complex dispersions: Effects of polymer structure, concentration and mixing conditions[J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2003, 218(1-3): 151～159.
[19] Kono K, Tabata F, Takagishi T. pH-responsive permeability of poly (acrylic acid) - poly (ethylenimine) complex capsule membrane[J]. Journal of Membrane Science, 1993, 76(2-3): 233～243.
[20] Kono K, Ohno T, Kumei T, et al. Permeability characteristic of polyelectrolyte complex capsule membranes: effect of preparation condition onpermeability[J]. Journal of Applied Polymer Science, 1996, 59(4): 687～693.
[21] Kwon I C, Bae Y H, Wan K S. Heparin release from polymer complex[J]. Journal of controlled release, 1994, 30(2): 155～159.
[22] Hari P R, Chandy T, Sharma C P. Chitosan/calcium-alginate beads for oral delivery of insulin[J]. Journal of Applied Polymer Science, 1996, 59(11): 1795～1801.
[23] Liu L, Liu S, Ng S, et al. Controlled release of interleukin-2 for tumour immunotherapy using alginate/chitosan porous microspheres[J]. Journal of Controlled Release, 1997, 43(1): 65～74.
[24] Muniruzzaman M, Tabata Y, Hijikata S, et al. Structural change of basic fibroblast growth factor through gelatin complexation[A]. Proceedings of the 1997 Boston Meeting[C]. Washington, DC, USA: ACS, 1998. 247～248.
[25] Muniruzzaman M, Tabata Y, Ikada Y. Physicochemical properties of basic fibroblast growth factor-gelatin complex[J]. Journal of Bioactive and Compatible Polymers, 2000, 15(5): 365～375.
[26] Hamano T, Chiba D, Teramoto A, et al. Adsorption of fibronectin, albumin and fibroblast growth factor-basic onto polyelectrolyte complex (PEC), which controls human periodontal ligament fibroblast (HPLF) proliferation and differentiation[J]. Journal of Macromolecular Science - Pure and Applied Chemistry, 1998, A35(10): 1681～1693.
[27] Hashida M, Takemura S, Nishikawa M, et al. Targeted delivery of plasmid DNA complexed with galactosylated poly(l-lysine)[J]. Journal of Controlled Release, 1998, 53(1): 301～310.
[28] Jagur-Grodzinski J. Polymers for tissue engineering, medical devices, and regenerative medicine. Concise general review of recent studies[J]. Polymers for Advanced Technologies, 2006, 17(6): 395～418.
[29] Agrawal C M, Ray R B. Biodegradable polymeric scaffolds for musculoskeletal tissue engineering[J]. Journal of Biomedical Materials Research, 2001, 55(2): 141～150.
[30] Lohbach C, Neumann D, Lehr C M, et al. Human vascular endothelial cells inprimary cell culture for the evaluation of nanoparticle bioadhesion[J]. Journal of Nanoscience and Nanotechnology, 2006, 6(9-10): 3303～3309.
[31] Teramoto A, Hachimori A, Abe K. Interaction of hepatocytes with polyelectrolyte complex(I): the effect of nonspecific interaction on adhesion of the cell[J]. Polymers for Advanced Technologies, 1999, 10(12): 695～701.
[32] Kotz J, Beitz S K. Self-assembled polyelectrolyte systems[J]. Progress in Polymer Science, 2001, 26(8): 1199～1232.
[33] Gohy J F, Varshney S K, Antoun S, et al. Water-soluble complexes formed by sodium poly(4-styrenesulfonate) and a poly(2-vinylpyridinium)-block-poly(ethyleneoxide) copolymer[J]. Macromolecules, 2000, 33(25): 9298～9305.
[34] F, rster S, Hermsdorf N, et al. Structure of polyelectrolyte block copolymer micelles[J]. Macromolecules, 2002, 35(10): 4096～4105.
[35] Bartkowiak A. Effect of the ionic strength on properties of binary alginate/oligochitosan microcapsules[J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2002, 204(1-3): 117～124.
[36] Hu Y, Jiang X, Ding Y, et al. Synthesis and characterization of Chitosan-poly(acrylic acid) nanoparticles[J]. Biomaterials, 2002, 23(15): 3193～3201.
[37] Mori H, Muller A H, Klee J E. Intelligent colloidal hybrids via reversible pH-induced complexation of polyelectrolyte and silica nanoparticles[J]. Journal of the American Chemical Society, 2003, 125(13): 3712～3713.
[38] Immaneni A, McHugh A J. Flow-induced conformational changes and phase behavior of aqueous poly- L-lysine solutions[J]. Biopolymers, 1998, 45(3): 239～246.
[39] Sfika V, Tsitsilianis C. Association phenomena of poly(acrylic acid)-b-poly(2-vinylpyridine)-b-poly(acrylic acid) triblock polyampholyte in aqueous solutions: From transient network to compact micelles[J]. Macromolecules, 2003, 36(13): 4983～4988.
[40] Decher G, Hong J. Buildup of ultrathin multilayer films by self-assemblyprocess. 1. Consecutive adsorption of anionic and cationic bipolar amphiphiles on charged surfaces[J]. Makromol. Chem., Macromol. Symp., 1991, 46(1): 321～328.
[41] Decher G. Fuzzy nanoassemblies: toward layered polymeric multicomposites[J]. Science, 1997, 277(5330): 1232～1237.
[42] Shen J, Zhang X, Sun Y. Molecular deposition films[J]. Progress in Natural Science, 1996, 6(6): 651～651.
[43] Zhang X, Shen J. Self-assembled ultrathin films: From layered nanoarchitectures to functional assemblies[J]. Advanced Materials, 1999, 11(13): 1139～1143.
[44] Ulman A. Formation and structure of self-assembled monolayers[J]. Chemical review, 1996, 96: 1533～1541.
[45] Kolarik L, Furlong D N, Joy H, et al. Building assemblies from high molecular weight polyelectrolytes[J]. Langmuir, 1999, 15(23): 8265～8275.
[46] Chen W, McCarthy T J. Layer-by-layer deposition: a tool for polymer surface modification[J]. Macromolecules, 1997, 30(1): 78～86.
[47] Kotov N A. Layer-by-layer self-assembly: the contribution of hydrophobic interactions[J]. Nanostructured Materials, 1999, 12(5): 789～796.
[48] Fischer P, Koetse M, Laschewsky A, et al. Orientation of nonlinear optical active dyes in electrostatically self-assembled polymer films containing cyclodextrins[J]. Macromolecules, 2000, 33(26): 9471～9473.
[49] Arys X, Laschewsky A, Jonas A M. Ordered polyelectrolyte "multilayers" - 1. Mechanisms of growth and structure formation: A comparison with classical fuzzy "multilayers"[J]. Macromolecules, 2001, 34(10): 3318～3330.
[50] Laurent D, Schlenoff J B. Multilayer Assemblies of Redox Polyelectrolytes[J]. Langmuir, 1997, 13(6): 1552～1557.
[51] Hoogeveen N G, Cohen S M, Fleer G J, et al. Formation and Stability of Multilayers of Polyelectrolytes[J]. Langmuir, 1996, 12(15): 3675～3681.
[52] Lvov Y, Ariga K, Ichinose I, et al. Assembly of Multicomponent Protein Films by Means of Electrostatic Layer-by-Layer Adsorption[J]. Journal of theAmerican Chemical Society, 1995, 117(22): 6117～6123.
[53] Radtchenko I L, Sukhorukov G B, Leporatti S, et al. Assembly of Alternated Multivalent Ion/Polyelectrolyte Layers on Colloidal Particles. Stability of the Multilayers and Encapsulation of Macromolecules into Polyelectrolyte Capsules[J]. Journal of Colloid and Interface Science, 2000, 230(2): 272～280.
[54] Fou A C, Rubner M F. Molecular-level processing of conjugated polymers. 2. Layer-by-layer manipulation of in-situ polymerized p-type doped conducting polymers[J]. Macromolecules, 1995, 28(21): 7115～7120.
[55] Sukhishvili S A. Responsive polymer films and capsules via layer-by-layer assembly[J]. Current Opinion in Colloid and Interface Science, 2005, 10(1-2): 37～44.
[56] Lavalle P, Vivet V, Jessel N, et al. Direct evidence for vertical diffusion and exchange processes of polyanions and polycations in polyelectrolyte multilayer films[J]. Macromolecules, 2004, 37(3): 1159～1162.
[57] Lavalle P, Picart C, Mutterer J, et al. Modeling the Buildup of Polyelectrolyte Multilayer Films Having Exponential Growth[J]. Journal of Physical Chemistry B, 2004, 108(2): 635～648.
[58] Messina R. Polyelectrolyte multilayering on a charged planar surface[J]. Macromolecules, 2004, 37(2): 621～629.
[59] Poptoshev E, Schoeler B, Caruso F. Influence of solvent quality on the growth of polyelectrolyte multilayers[J]. Langmuir, 2004, 20(3): 829～834.
[60] Serizawa T, Goto H, Kishida T, et al. Improved alternate deposition of biodegradable naturally occurring polymers onto a quartz crystal microbalance[J]. Journal of Polymer Science, Part A: Polymer Chemistry, 1999, 37(6): 801～804.
[61] Hiller J A, Rubner M F. Reversible molecular memory and pH-switchable swelling transitions in polyelectrolyte multilayers[J]. Macromolecules, 2003, 36(11): 4078～4083.
[62] Yang S Y, Mendelsohn J D, Rubner M F. New class of ultrathin, highly cell-adhesion-resistant polyelectrolyte multilayers with micropatterningcapabilities[J]. Biomacromolecules, 2003, 4(4): 987～994.
[63] Yoshihiro I, Kazuhiko N, Eisaku L, et al. Fluorescence study of polyelectrolyte complex formation: 2. Effect of acidity of polyanions on complexation[J]. Polymer, 1992, 33(14): 3016～3023.
[64] Dubas S T, Schlenoff J B. Factors Controlling the Growth of Polyelectrolyte Multilayers[J]. Macromolecules, 1999, 32(24): 8153～8160.
[65] Salom, ki M, Vinokurov I A, et al. Effect of temperature on the buildup of polyelectrolyte multilayers[J]. Langmuir, 2005, 21(24): 11232～11240.
[66] Itoh Y, Matsusaki M, Kida T, et al. Enzyme-responsive release of encapsulated proteins from biodegradable hollow capsules[J]. Biomacromolecules, 2006, 7(10): 2715～2718.
[67] De G B, Dejugnat C, Verhoeven E, et al. Layer-by-layer coating of degradable microgels for pulsed drug delivery[J]. Journal of Controlled Release, 2006, 116(2 SPEC ISS): 159～169.
[68] Moya S E, Toca-Herrera J L. From hollow shells to artificial cells: Biointerface engineering on polyelectrolyte capsules[J]. Journal of Nanoscience and Nanotechnology, 2006, 6(8): 2329～2337.
[69] DeLongchamp D M, Kastantin M, Hammond P T. High-contrast electrochromism from layer-by-layer polymer films[J]. Chemistry of Materials, 2003, 15(8): 1575～1586.
[70] Cho J, Char K, Young K D. Change in the quantum efficiency due to relative thickness variation of hole transport and emitting layers in a self-assembled device[J]. Thin Solid Films, 2002, 415(1-2): 303～307.
[71] Han S, Briseno A L, Shi X, et al. Polyelectrolyte-coated nanosphere lithographic patterning of surfaces: Fabrication and characterization of electropolymerized thin polyaniline honeycomb films[J]. Journal of Physical Chemistry B, 2002, 106(25): 6465～6472.
[72] Dayang W, Caruso R A, Caruso F. Synthesis of macroporous titania and inorganic composite materials from coated colloidal spheres-a novel route to tunepore morphology[J]. Chemistry of Materials, 2001, 13(2): 364～371.
[73] Tieke B, Toutianoush A, Jin W. Selective transport of ions and molecules across layer-by-layer assembled membranes of polyelectrolytes, p-sulfonato-calix[n]arenes and Prussian Blue-type complex salts[J]. Advances in Colloid and Interface Science, 2005, 116(1-3): 121～131.
[74] Caruso F, Donath E, Moehwald H. Influence of polyelectrolyte multilayer coatings on Foerster resonance energy transfer between 6-carboxyfluorescein and rhodamine B-labeled particles in aqueous solution[J]. Journal of Physical Chemistry B, 1998, 102(11): 2011～2016.
[75] Donath E, Walther D, Shilov V N, et al. Nonlinear hairy layer theory of electrophoretic fingerprinting applied to consecutive layer by layer polyelectrolyte adsorption onto charged polystyrene latex particles[J]. Langmuir, 1997, 13(20): 5294～5305.
[76] Johnston A P, Cortez C, Angelatos A S, et al. Layer-by-layer engineered capsules and their applications[J]. Current Opinion in Colloid and Interface Science, 2006, 11(4): 203～209.
[77] Donath E, Sukhorukov G B, Caruso F, et al. Novel Hollow Polymer Shells by Colloid-Templated Assembly of Polyelectrolytes[J]. Angewandte Chemie International Edition, 1998, 37(16): 2201～2205.
[78] Caruso R A, Susha A, Caruso F. Multilayered Titania, Silica, and Laponite Nanoparticle Coatings on Polystyrene Colloidal Templates and Resulting Inorganic Hollow Spheres[J]. Chemistry of Materials, 2001, 13(2): 400～409.
[79] Changyou G S. Melamine Formaldehyde Core Decomposition as the Key Step Controlling Capsule Integrity: Optimizing the Polyelectrolyte Capsule Fabrication[J]. Macromolecular Chemistry and Physics, 2002, 203(7): 953～960.
[80] Gao C, Mohwald H, Shen J. Soluble microcapsules assembled stepwise from weak polyelectrolytes using acid-decomposable cores[J]. Advanced Materials, 2003, 15(11): 930～933.
[81] Tong W, Gao C. Multilayer microcapsules with tailored structures forbio-related applications[J]. Journal of Materials Chemistry, 2008, 18(32): 3799～3812.
[82] Sukhorukov G B, Donath E, Davis S, et al. Stepwise polyelectrolyte assembly on particle surfaces: a novel approach to colloid design[J]. Polymers for Advanced Technologies, 1998, 9(10-11): 759～767.
[83] Zhu Y, Gao C, He T, et al. Layer-by-layer assembly to modify poly(L-lactic acid) surface toward improving its cytocompatibility to human endothelial cells[J]. Biomacromolecules, 2003, 4(2): 446～452.
[84] Itoh Y, Matsusaki M, Kida T, et al. Enzyme-responsive release of encapsulated proteins from biodegradable hollow capsules[J]. Biomacromolecules, 2006, 7(10): 2715～2718.
[85] Zhu Y, Shi J, Shen W, et al. Stimuli-responsive controlled drug release from a hollow mesoporous silica sphere/polyelectrolyte multilayer core-shell structure[J]. Angewandte Chemie - International Edition, 2005, 44(32): 5083～5087.
[86] Han B, Shen B, Wang Z, et al. Layered microcapsules for daunorubicin loading and release as well as in vitro and in vivo studies[J]. Polymers for Advanced Technologies, 2008, 19(1): 36～46.
[87] Leporatti S, Gao C, Voigt A, et al. Shrinking of ultrathin polyelectrolyte multilayer capsules upon annealing: A confocal laser scanning microscopy and scanning force microscopy study[J]. European Physical Journal E, 2001, 5(1): 13～20.
[88] Leporatti S, Voigt A, Mitl, et al. Scanning force microscopy investigation of polyelectrolyte nano- and microcapsule wall texture[J]. Langmuir, 2000, 16(9): 4059～4063.
[89] Gao C, Leporatti S, Donath E, et al. Surface texture of poly(styrenesulfonate sodium salt) and poly(diallyldimethylammonium chloride) micron-sized multilayer capsules: A scanning force and confocal microscopy study[J]. Journal of Physical Chemistry B, 2000, 104(30): 7144～7149.
[90] Qiu X, Leporatti S, Donath E, et al. Studies on the drug release properties of polysaccharide multilayers encapsulated ibuprofen microparticles[J]. Langmuir,2001, 17(17): 5375～5380.
[91] Balabushevitch N G, Sukhorukov G B, Moroz N A, et al. Encapsulation of proteins by layer-by-layer adsorption of polyelectrolytes onto protein aggregates: Factors regulating the protein release[J]. Biotechnology and Bioengineering, 2001, 76(3): 207～213.
[92] Caruso F, Trau D, Moehwald H, et al. Enzyme encapsulation in layer-by-layer engineered polymer multilayer capsules[J]. Langmuir, 2000, 16(4): 1485～1488.
[93] Cao C, Liu X, Shen J, et al. Spontaneous deposition of horseradish peroxidase into polyelectrolyte multilayer capsules to improve its activity and stability[J]. Chemical Communication, 2002, (17): 1928～1929.
[94] Dahne L, Leporatti S, Donath E, et al. Fabrication of micro reaction cages with tailored properties[J]. Journal of the American Chemical Society, 2001, 123(23): 5431～5436.
[95] Gaponik N, Radtchenko I L, Sukhorukov G B, et al. Toward encoding combinatorial libraries: Charge-driven microencapsulation of semiconductor nanocrystals luminescing in the visible and near IR[J]. Advanced Materials, 2002, 14(12): 879～882.
[96] Chuang C Y, Don T M, Chiu W Y. Synthesis and properties of chitosan-modified poly(acrylic acid)[J]. Journal of Applied Polymer Science, 2008, 109(5): 3382～3389.
[97] Hajdu I, Bodnar M, Filipcsei G, et al. Nanoparticles prepared by self-assembly of Chitosan and poly-γ-glutamic acid[J]. Colloid and Polymer Science, 2008, 286(3): 343～350.
[98] Tian Y, Bromberg L, Lin S N, et al. Complexation and release of doxorubicin from its complexes with pluronic P85-b-poly(acrylic acid) block copolymers[J]. Journal of Controlled Release, 2007, 121(3): 137～145.
[99] Veronese F M, Morpurgo M. Bioconjugation in pharmaceutical chemistry[J]. II Farmaco, 1999, 54(8): 497～516.
[100] Miyata K, Kakizawa Y, Nishiyama N, et al. Freeze-dried formulations for in vivo gene delivery of PEGylated polyplex micelles with disulfide crosslinked coresto the liver[J]. Journal of Controlled Release, 2005, 109(1-3): 15～23.
[101] Fwu-Long M S. Chitosan-Polyelectrolyte complexation for the preparation of gel beads and controlled release of anticancer drug. I. Effect of phosphorous polyelectrolyte complex and enzymatic hydrolysis of polymer[J]. Journal of Applied Polymer Science, 1999, 74(7): 1868～1879.
[102] Fwu-Long M S. Chitosan-polyelectrolyte complexation for the preparation of gel beads and controlled release of anticancer drug. II. Effect of pH-dependent ionic crosslinking or interpolymer complex using tripolyphosphate or polyphosphate as reagent[J]. Journal of Applied Polymer Science, 1999, 74(5): 1093～1107.
[103] Haidar Z S, Hamdy R C, Tabrizian M. Protein release kinetics for core-shell hybrid nanoparticles based on the layer-by-layer assembly of alginate and chitosan on liposomes[J]. Biomaterials, 2008, 29(9): 1207～1215.
[104] Li C. Poly(L-glutamic acid)–anticancer drug conjugates[J]. Advanced Drug Delivery Reviews, 2002, 54(5): 695～713.
[105] Peniche C, Arguelles-Monal W, Peniche H, et al. Chitosan: An Attractive Biocompatible Polymer for Microencapsulation[J]. Macromolecular Bioscience, 2003, 3(10): 511～520.
[106]曹田,尹静波,罗坤,等.高分子量的聚L-谷氨酸的合成与表征[J].高等学校化学学报, 2006, 27(2): 369～371.
[107]谢勇涛,尹静波,赵长稳,等.聚谷氨酸苄酯脱保护制备聚L-谷氨酸的正交实验研究[J].高等学校化学学报, 2008, 29(1): 197～200.
[108] Lavasanifar A, Samuel J, Kwon G S. Poly(ethylene oxide)-block-poly(-amino acid) micelles for drug delivery[J]. Advanced Drug Delivery Reviews, 2002, 54(2): 169～190.
[109]张国林,吴秋华,潘彤, et al. AB型两亲聚L-谷氨酸-苄酯-聚乙二醇嵌段共聚物的合成与表征[J].高分子学报, 2004, (2): 223～227.
[110]王琴梅,潘仕荣,等.聚谷氨酸苄酯—聚乙二醇嵌段共聚物的合成和表征[J].功能高分子学报, 2001, 14(1): 61～65.
[111] Deng M, Wang R, Rong G, et al. Synthesis of a novel structural triblockcopolymer of poly(γ-benzyl-L-glutamic acid)-b-poly(ethylene oxide)-b-poly(ε-caprolactone)[J]. Biomaterials, 2004, 25(17): 3553～3558.
[112] Guan H, Xie Z, Zhang P, et al. Synthesis and Characterization of Biodegradable Amphiphilic Triblock Copolymers Containing L-Glutamic Acid Units[J]. Biomacromolecules, 2005, 6(4): 1954～1960.
[113] Wang L Y, Wang S G, Bei J Z. Synthesis and characterization of macroinitiator-amino terminated PEG and poly(γ-benzyl-L-glutamate)-PEO-poly(γ-benzyl-L-glutamate triblock copolymer[J]. Polymers for Advanced Technologies, 2004, 15(10): 617～621.
[114] Deng C, Rong G, Tian H, et al. Synthesis and characterization of poly(ethylene glycol)-b-poly (L-lactide)-b-poly(L-glutamic acid) triblock copolymer[J]. Polymer, 2005, 46(3): 653～659.
[115] Deng C, Tian H, Zhang P, et al. Synthesis and Characterization of RGD Peptide Grafted Poly(ethylene glycol)-b-Poly(L-lactide)-b-Poly(L-glutamic acid) Triblock Copolymer[J]. Biomacromolecules, 2006, 7(2): 590～596.
[116] Matralis A, Sotiropoulou M, Bokias G, et al. Water-soluble stoichiometric polyelectrolyte complexes based on cationic comb-type copolymers[J]. Macromolecular Chemistry and Physics, 2006, 207(12): 1018～1025.
[117]项茂良,江明.多组分聚合物体系中的相容和络合[J].高分子通报, 1997, (1): 15～21.
[118]陈俊燕,项茂良,江明.由特殊相互作用导致的高分子间的络合Ⅸ.聚(苯乙烯-co-4-乙烯基苯酚)/聚(苯乙烯-co-4-乙烯基吡啶)在本体中的相容-络合行为[J].高分子学报, 1999, (5): 545～550.
[119] de Vasconcelos C L, Bezerril P M, dos Santos D, et al. Effect of Molecular Weight and Ionic Strength on the Formation of Polyelectrolyte Complexes Based on Poly(methacrylic acid) and Chitosan[J]. Biomacromolecules, 2006, 7(4): 1245～1252.
[120] Ward C M, Fisher K D, Seymour L W. Turbidometric analysis of polyelectrolyte complexes formed between poly(L-lysine) and DNA[J]. Colloidsand Surfaces B: Biointerfaces, 1999, 16(1): 253～260.
[121] Hartlig S M, Carlesso G, Davidson J M, et al. Development of improve nanoparticle polyelectrolyte complex physicochemistry by nonstoichiometric mixing of polyions with similar molecular weights[J]. Biomacromolecules, 2007, 8(1): 265～272.
[122] Katayose S, Kataoka K. Water-Soluble Polyion Complex Associates of DNA and Poly(ethylene glycol)-Poly(L-lysine) Block Copolymer[J]. Bioconjugate Chemistry, 1997, 8(5): 702～707.
[123] Bronich T K, Kabanov A V. Soluble Complexes from Poly(ethylene oxide)-block-polymethacrylate Anions and N-Alkylpyridinium Cations[J]. Macromolecules, 1997, 30(12): 3519～3525.
[124] Schwarz S, Jaeger W, Bratskaya S, et al. Formation of polyelectrolyte complexes in a polycarboxybetaine/weak polyanion system[J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2006, 276(1-3): 65～71.
[125] Harada A, Kataoka K. Formation of Polyion Complex Micelles in an Aqueous Milieu from a Pair of Oppositely-Charged Block Copolymers with Poly(ethylene glycol) Segments[J]. Macromolecules, 1995, 28(15): 5294～5299.
[126] Gohy J F, Varshney S K, Jerome R. Water-Soluble Complexes Formed by Poly(2-vinylpyridinium)-block-poly(ethylene oxide) and Poly(sodium methacrylate)-block-poly(ethylene oxide) Copolymers[J]. Macromolecules, 2001, 34(10): 3361～3366.
[127] Chelushkin P S, Lysenko E A, Bronich T K, et al. Polyion complex nanomaterials from block polyelectrolyte micelles and linear polyelectrolytes of opposite charge: 1. Solution behavior[J]. Journal of Physical Chemistry B, 2007, 111(29): 8419～8425.
[128] Hofs B, De K A, Stuart M A. On the stability of (highly aggregated) polyelectrolyte complexes containing a charged-block-neutral diblock copolymer[J]. Journal of Physical Chemistry B, 2007, 111(20): 5621～5627.
[129] Kabanov A V, Bronich T K, Kabanov V A, et al. Soluble Stoichiometric Complexes from Poly(N-ethyl-4-vinylpyridinium) Cations and Poly(ethyleneoxide)-block-polymethacrylate Anions[J]. Macromolecules, 1996, 29(21): 6797～6802.
[130] Vinogradov S V, Bronich T K, Kabanov A V. Self-Assembly of Polyamine-Poly(ethylene glycol) Copolymers with Phosphorothioate Oligonucleotides[J]. Bioconjugate Chemistry, 1998, 9(6): 805～812.
[131] Harada A, Kataoka K. Chain length recognition: core-shell supramolecular assembly from oppositely charged block copolymers[J]. Science, 1999, 283(5398): 65～67.
[132] Kabanov A V, Bronich T K, Kabanov V A, et al. Soluble Stoichiometric Complexes from Poly(N-ethyl-4-vinylpyridinium) Cations and Poly(ethylene oxide)-block-polymethacrylate Anions[J]. Macromolecules, 1996, 29(21): 6797～6802.
[133] Kondo T, Sawatari C, Manley R S, et al. Characterization of hydrogen bonding in cellulose-synthetic polymer blend systems with regioselectively substituted methylcellulose[J]. Macromolecules, 1994, 27(1): 210～215.
[134] Kolhe P, Kannan R M. Improvement in ductility of chitosan through blending and copolymerization with PEG: FTIR investigation of molecular interactions[J]. Biomacromolecules, 2003, 4(1): 173～180.
[135] Zeng M, Fang Z, Xu C. Effect of compatibility on the structure of the microporous membrane prepared by selective dissolution of chitosan/synthetic polymer blend membrane[J]. Journal of Membrane Science, 2004, 230(1-2): 175～181.
[136] Luo K, Yin J, Song Z, et al. Biodegradable Interpolyelectrolyte Complexes Based on Methoxy Poly(ethylene glycol)-b-poly(α,l-glutamic acid) and Chitosan[J]. Biomacromolecules, 2008, 9(10): 2653～2661.
[137] Rosca C, Popa M I, Lisa G, et al. Interaction of chitosan with natural or synthetic anionic polyelectrolytes. 1. The chitosan-carboxymethylcellulose complex[J]. Carbohydrate Polymers, 2005, 62(1): 35～41.
[138] Fan L, Du Y, Zhang B, et al. Preparation and properties of alginate/carboxymethyl chitosan blend fibers[J]. Carbohydrate Polymers, 2006,65(4): 447～452.
[139] Luo K, Yin J, Khutoryanskaya O V, et al. Mucoadhesive and Elastic Films Based on Blends of Chitosan and Hydroxyethylcellulose[J]. Macromolecular Bioscience, 2008, 8(2): 184～192.
[140] He Y, Zhu B, Inoue Y. Hydrogen bonds in polymer blends[J]. Progress in Polymer Science, 2004, 29(10): 1021～1051.
[141] Lau C, Mi Y. A study of blending and complexation of poly(acrylic acid)/poly(vinyl pyrrolidone)[J]. Polymer, 2002, 43(3): 823～829.
[142] Huglin M B, Rego J M, Gooda S R. Comments on thermal transitions in some polyelectrolyte complexes[J]. Macromolecules, 1990, 23(26): 5359～5361.
[143] Huglin M B, Webster L, Robb I D. Complex formation between poly(4-vinylpyridinium chloride) and poly[sodium(2-acrylamido-2-methyl propane sulfonate)] in dilute aqueous solution[J]. Polymer, 1996, 37(7): 1211～1215.
[144] Smitha B, Sridhar S, Khan A A. Polyelectrolyte complexes of chitosan and poly(acrylic acid) as proton exchange membranes for fuel cells[J]. Macromolecules, 2004, 37(6): 2233～2239.
[145] Fang L, Goh S H. Miscible chitosan/tertiary amide polymer blends[J]. Journal of Applied Polymer Science, 2000, 76(12): 1785～1790.
[146] Lee S J, Kim S S, Lee Y M. Interpenetrating polymer network hydrogels based on poly(ethylene glycol) macromer and chitosan[J]. Carbohydrate Polymers, 2000, 41(2): 197～205.
[147] Yang J, Zhao T, Cui J, et al. Nonisothermal crystallization behavior of the poly(ethylene glycol) block in poly(L-lactide)poly(ethylene glycol) diblock copolymers: Effect of the poly(L-lactide) block length[J]. Journal of Polymer Science, Part B: Polymer Physics, 2006, 44(22): 3215～3226.
[148] Huang C I, Tsai S H, Chen C M. Isothermal crystallization behavior of poly(L-lactide) in poly(L-lactide)-block-poly(ethylene glycol) diblock copolymers[J]. Journal of Polymer Science, Part B: Polymer Physics, 2006, 44(17): 2438～2448.
[149] Rambo B M, Lavigne J J. Defining self-assembling linearoligo(dioxaborole)s[J]. Chemistry of Materials, 2007, 19(15): 3732～3739.
[150] Wang Y, Angelatos A S, Caruso F. Template synthesis of nanostructured materials via layer-by-layer assembly[J]. Chemistry of Materials, 2008, 20(3): 848～858.
[151] Stockton W B, Rubner M F. Molecular-Level Processing of Conjugated Polymers. 4. Layer-by-Layer Manipulation of Polyaniline via Hydrogen-Bonding Interactions[J]. Macromolecules, 1997, 30(9): 2717.
[152] Richert L, Lavalle P, Payan E, et al. Layer by Layer Buildup of Polysaccharide Films: Physical Chemistry and Cellular Adhesion Aspects[J]. Langmuir, 2004, 20(2): 448～458.
[153] Lavalle P, Gergely C, Cuisinier F J, et al. Comparison of the structure of polyelectrolyte multilayer films exhibiting a linear and an exponential growth regime: An in situ atomic force microscopy study[J]. Macromolecules, 2002, 35(11): 4458～4465.
[154]余海湖.静电自组装纳米复合薄膜研究[博士].武汉:武汉理工大学, 2002.
[155]李家值.半导体化学原理[M].北京:科学出版社, 1980.
[156] Li Q L, Chen Z Q, Darvell B W, et al. Chitosan-phosphorylated chitosan polyelectrolyte complex hydrogel as an osteoblast carrier[J]. Journal of Biomedical Materials Research - Part B Applied Biomaterials, 2007, 82(2): 481～486.
[157] Boulmedais F, Frisch B, Etienne O, et al. Polyelectrolyte multilayer films with pegylated polypeptides as a new type of anti-microbial protection for biomaterials[J]. Biomaterials, 2004, 25(11): 2003～2011.
[158] Picart C, Lavalle P, Hubert P, et al. Buildup mechanism for poly(L-lysine)/hyaluronic acid films onto a solid surface[J]. Langmuir, 2001, 17(23): 7414～7424.
[159] Elbert D L, Herbert C B, Hubbell J A. Thin polymer layers formed by polyelectrolyte multilayer techniques on biological surfaces[J]. Langmuir, 1999, 15(16): 5355～5362.
[160] Ruths J, Essler F, Decher G, et al. Polyelectrolytes. I: Polyanion/polycationmultilayers at the air/monolayer/water interface as elements for quantitative polymer adsorption studies and preparation of hetero-superlattices on solid surfaces[J]. Langmuir, 2000, 16(23): 8871～8878.
[161] Ladam G, Schaad P, Voegel J C, et al. In situ determination of the structural properties of initially deposited polyelectrolyte multilayers[J]. Langmuir, 2000, 16(3): 1249～1255.
[162] Lavalle P, Gergely C, Cuisinier F J, et al. Comparison of the structure of polyelectrolyte multilayer films exhibiting a linear and an exponential growth regime: An in situ atomic force microscopy study[J]. Macromolecules, 2002, 35(11): 4458～4465.
[163] Miyashita N, M, hwald H, et al. 2D structure of unsaturated fatty acid amide mono- and multilayer on graphite: Self-assembly and thermal behavior[J]. Chemistry of Materials, 2007, 19(17): 4259～4262.
[164] Yoo D, Shiratori S S, Rubner M F. Controlling Bilayer Composition and Surface Wettability of Sequentially Adsorbed Multilayers of Weak Polyelectrolytes[J]. Macromolecules, 1998, 31(13): 4309～4318.
[165] Shiratori S S, Rubner M F. pH-dependent thickness behavior of sequentially adsorbed layers of weak polyelectrolytes[J]. Macromolecules, 2000, 33(11): 4213～4219.
[166] Wang X, Kim H J, Xu P, et al. Biomaterial coatings by stepwise deposition of silk fibroin[J]. Langmuir, 2005, 21(24): 11335～11341.
[167] Flexer V, Forzani E S, Calvo E J, et al. Structure and thickness dependence of "molecular wiring" in nanostructured enzyme multilayers[J]. Analytical Chemistry, 2006, 78(2): 399～407.
[168] Ulbrich K, Subr V. Polymeric anticancer drugs with pH-controlled activation[J]. Advanced Drug Delivery Reviews, 2004, 56(7): 1023～1050.
[169] Zhu L, Ma J, Jia N, et al. Chitosan-coated magnetic nanoparticles as carriers of 5-Fluorouracil: Preparation, characterization and cytotoxicity studies[J]. Colloids and Surfaces B: Biointerfaces, 2009, 68(1): 1～6.
[170]郑爱萍,刘海宏,李宏斌,等. 5-氟脲嘧啶壳聚糖微球的制备及体外释放特性[J].中国药科大学学报, 2004, 35(4): 318～323.
[171]李可欣,陈大为,赵秀丽,等.分散-交联法制备氟尿嘧啶壳聚糖微球的研究[J].中国药学杂志, 2005, 40(18): 1392～1395.
[172]王怀玉,董利民,昝青峰,等.乳化交联法制备壳聚糖微球粘连原因分析[J].功能材料, 2007, 38(A05): 1923～1925.
[173] Schoeler B, Kumaraswamy G, Caruso F. Investigation of the influence of polyelectrolyte charge density on the growth of multilayer thin films prepared by the layer-by-layer technique[J]. Macromolecules, 2002, 35(3): 889～897.
[174] Milkova V, Radeva T. Effect of chain length and charge density on the construction of polyelectrolyte multilayers on colloidal particles[J]. Journal of Colloid and Interface Science, 2007, 308(2): 300～308.
[175] Grigoriev D O, Bukreeva T, Mohwald H, et al. New Method for Fabrication of Loaded Micro- and Nanocontainers: Emulsion Encapsulation by Polyelectrolyte Layer-by-Layer Deposition on the Liquid Core[J]. Langmuir, 2008, 24(3): 999～1004.
[176] Zhao Q, Han B, Wang Z, et al. Hollow chitosan-alginate multilayer microcapsules as drug delivery vehicle: doxorubicin loading and in vitro and in vivo studies[J]. Nanomedicine: Nanotechnology, Biology, and Medicine, 2007, 3(1): 63～74.
[177]刘亚军,朱以华,张素秋,等.单分散三聚氰胺甲醛微球的制备[J].功能高分子学报, 2004, 17(1): 113～118.
[178] Al H, Gao J. Size-controlled polyelectrolyte nanocapsules via layer-by-layer self-assembly[J]. Journal of Materials Science, 2004, 39(4): 1429～1432.
[179] Gupta K C, Jabrail F H. Glutaraldehyde and glyoxal cross-linked chitosan microspheres for controlled delivery of centchroman[J]. Carbohydrate Research, 2006, 341(6): 744～756.
[2] Pasut G, Veronese F M. Polymer-drug conjugation, recent achievements and general strategies[J]. Progress in Polymer Science, 2007, 32(8-9): 933～961.
[3] Nishiyama N, Kataoka K. Current state, achievements, and future prospects of polymeric micelles as nanocarriers for drug and gene delivery[J]. Pharmacology & Therapeutics, 2006, 112(3): 630～648.
[4] Dai Z, Yin J, Yan S, et al. Polyelectrolyte complexes based on chitosan and poly(α,L-glutamic acid)[J]. Polymer International, 2007, 56(9): 1122～1127.
[5] Krol S, Del G S, Grupillo M, et al. Multilayer nanoencapsulation. new approach for immune protection of human pancreatic islets[J]. Nano Letters, 2006, 6(9): 1933～1939.
[6] Jewell C M, Zhang J, Fredin N J, et al. Release of plasmid DNA from intravascular stents coated with ultrathin multilayered polyelectrolyte films[J]. Biomacromolecules, 2006, 7(9): 2483～2491.
[7] Philipp B, Dautzenberg H, Linow K J, et al. Polyelectrolyte complexes. Recent developments and open problems[J]. Progress in Polymer Science (Oxford), 1989, 14(1): 91～172.
[8] Th A F, M M, Dautzenberg H, et al. Polyelectrolyte Complexes[J]. Advances in Polymer Science, 2004, 166(1): 113～171.
[9] Tsuchida E, Abe K, Honma M. Aggregation of Polyion Complexes between Synthetic Polyelectrolytes[J]. Macromolecules, 1976, 9(1): 112～117.
[10] Nikolaeva O, Budtova T, Alexeev V, et al. Interpolymer complexation between polyacrylic acid and cellulose ethers: Formation and properties[J]. Journal of Polymer Science, Part B: Polymer Physics, 2000, 38(10): 1323～1330.
[11] Mekhloufi G, Sanchez C, Renard D, et al. PH-induced structural transitions during complexation and coacervation of β-lactoglobulin and acacia gum[J].Langmuir, 2005, 21(1): 386～394.
[12] Dautzenberg H. Polyelectrolyte Complex Formation in Highly Aggregating Systems. 1. Effect of Salt: Polyelectrolyte Complex Formation in the Presence of NaCl[J]. Macromolecules, 1997, 30(25): 7810～7815.
[13] Karibyants N, Dautzenberg H, Coelfen H. Characterization of PSS/PDADMAC-co-AA polyelectrolyte complexes and their stoichiometry using analytical ultracentrifugation[J]. Macromolecules, 1997, 30(25): 7803～7809.
[14] Karibyants N, Dautzenberg H. Preferential binding with regard to chain length and chemical structure in the reactions of formation of quasi-soluble polyelectrolyte complexes[J]. Langmuir, 1998, 14(16): 4427～4434.
[15] Schatz C, Lucas J -, Viton C, et al. Formation and properties of positively charged colloids based on polyelectrolyte complexes of biopolymers[J]. Langmuir, 2004, 20(18): 7766～7778.
[16] Starodubtsev S G, Dembo A T, Dembo K A. Effect of Polymer Charge Density and Ionic Strength on the Formation of Complexes between Sodium Arylamido-2-methyl-1-propane-sulfonate-co-acrylamide Gels and Cetylpyridinium Chloride[J]. Langmuir, 2004, 20(16): 6599～6604.
[17] Hugerth A, Caram-Lelham N, Sundelof L O. The Effect of charge density and conformation on the polyelectrolyte complex formation between carrageenan and chitosan[J]. Carbohydrate Polymers, 1997, 34(3): 149～156.
[18] Buchhammer H M, Mende M, Oelmann M. Formation of mono-sized polyelectrolyte complex dispersions: Effects of polymer structure, concentration and mixing conditions[J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2003, 218(1-3): 151～159.
[19] Kono K, Tabata F, Takagishi T. pH-responsive permeability of poly (acrylic acid) - poly (ethylenimine) complex capsule membrane[J]. Journal of Membrane Science, 1993, 76(2-3): 233～243.
[20] Kono K, Ohno T, Kumei T, et al. Permeability characteristic of polyelectrolyte complex capsule membranes: effect of preparation condition onpermeability[J]. Journal of Applied Polymer Science, 1996, 59(4): 687～693.
[21] Kwon I C, Bae Y H, Wan K S. Heparin release from polymer complex[J]. Journal of controlled release, 1994, 30(2): 155～159.
[22] Hari P R, Chandy T, Sharma C P. Chitosan/calcium-alginate beads for oral delivery of insulin[J]. Journal of Applied Polymer Science, 1996, 59(11): 1795～1801.
[23] Liu L, Liu S, Ng S, et al. Controlled release of interleukin-2 for tumour immunotherapy using alginate/chitosan porous microspheres[J]. Journal of Controlled Release, 1997, 43(1): 65～74.
[24] Muniruzzaman M, Tabata Y, Hijikata S, et al. Structural change of basic fibroblast growth factor through gelatin complexation[A]. Proceedings of the 1997 Boston Meeting[C]. Washington, DC, USA: ACS, 1998. 247～248.
[25] Muniruzzaman M, Tabata Y, Ikada Y. Physicochemical properties of basic fibroblast growth factor-gelatin complex[J]. Journal of Bioactive and Compatible Polymers, 2000, 15(5): 365～375.
[26] Hamano T, Chiba D, Teramoto A, et al. Adsorption of fibronectin, albumin and fibroblast growth factor-basic onto polyelectrolyte complex (PEC), which controls human periodontal ligament fibroblast (HPLF) proliferation and differentiation[J]. Journal of Macromolecular Science - Pure and Applied Chemistry, 1998, A35(10): 1681～1693.
[27] Hashida M, Takemura S, Nishikawa M, et al. Targeted delivery of plasmid DNA complexed with galactosylated poly(l-lysine)[J]. Journal of Controlled Release, 1998, 53(1): 301～310.
[28] Jagur-Grodzinski J. Polymers for tissue engineering, medical devices, and regenerative medicine. Concise general review of recent studies[J]. Polymers for Advanced Technologies, 2006, 17(6): 395～418.
[29] Agrawal C M, Ray R B. Biodegradable polymeric scaffolds for musculoskeletal tissue engineering[J]. Journal of Biomedical Materials Research, 2001, 55(2): 141～150.
[30] Lohbach C, Neumann D, Lehr C M, et al. Human vascular endothelial cells inprimary cell culture for the evaluation of nanoparticle bioadhesion[J]. Journal of Nanoscience and Nanotechnology, 2006, 6(9-10): 3303～3309.
[31] Teramoto A, Hachimori A, Abe K. Interaction of hepatocytes with polyelectrolyte complex(I): the effect of nonspecific interaction on adhesion of the cell[J]. Polymers for Advanced Technologies, 1999, 10(12): 695～701.
[32] Kotz J, Beitz S K. Self-assembled polyelectrolyte systems[J]. Progress in Polymer Science, 2001, 26(8): 1199～1232.
[33] Gohy J F, Varshney S K, Antoun S, et al. Water-soluble complexes formed by sodium poly(4-styrenesulfonate) and a poly(2-vinylpyridinium)-block-poly(ethyleneoxide) copolymer[J]. Macromolecules, 2000, 33(25): 9298～9305.
[34] F, rster S, Hermsdorf N, et al. Structure of polyelectrolyte block copolymer micelles[J]. Macromolecules, 2002, 35(10): 4096～4105.
[35] Bartkowiak A. Effect of the ionic strength on properties of binary alginate/oligochitosan microcapsules[J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2002, 204(1-3): 117～124.
[36] Hu Y, Jiang X, Ding Y, et al. Synthesis and characterization of Chitosan-poly(acrylic acid) nanoparticles[J]. Biomaterials, 2002, 23(15): 3193～3201.
[37] Mori H, Muller A H, Klee J E. Intelligent colloidal hybrids via reversible pH-induced complexation of polyelectrolyte and silica nanoparticles[J]. Journal of the American Chemical Society, 2003, 125(13): 3712～3713.
[38] Immaneni A, McHugh A J. Flow-induced conformational changes and phase behavior of aqueous poly- L-lysine solutions[J]. Biopolymers, 1998, 45(3): 239～246.
[39] Sfika V, Tsitsilianis C. Association phenomena of poly(acrylic acid)-b-poly(2-vinylpyridine)-b-poly(acrylic acid) triblock polyampholyte in aqueous solutions: From transient network to compact micelles[J]. Macromolecules, 2003, 36(13): 4983～4988.
[40] Decher G, Hong J. Buildup of ultrathin multilayer films by self-assemblyprocess. 1. Consecutive adsorption of anionic and cationic bipolar amphiphiles on charged surfaces[J]. Makromol. Chem., Macromol. Symp., 1991, 46(1): 321～328.
[41] Decher G. Fuzzy nanoassemblies: toward layered polymeric multicomposites[J]. Science, 1997, 277(5330): 1232～1237.
[42] Shen J, Zhang X, Sun Y. Molecular deposition films[J]. Progress in Natural Science, 1996, 6(6): 651～651.
[43] Zhang X, Shen J. Self-assembled ultrathin films: From layered nanoarchitectures to functional assemblies[J]. Advanced Materials, 1999, 11(13): 1139～1143.
[44] Ulman A. Formation and structure of self-assembled monolayers[J]. Chemical review, 1996, 96: 1533～1541.
[45] Kolarik L, Furlong D N, Joy H, et al. Building assemblies from high molecular weight polyelectrolytes[J]. Langmuir, 1999, 15(23): 8265～8275.
[46] Chen W, McCarthy T J. Layer-by-layer deposition: a tool for polymer surface modification[J]. Macromolecules, 1997, 30(1): 78～86.
[47] Kotov N A. Layer-by-layer self-assembly: the contribution of hydrophobic interactions[J]. Nanostructured Materials, 1999, 12(5): 789～796.
[48] Fischer P, Koetse M, Laschewsky A, et al. Orientation of nonlinear optical active dyes in electrostatically self-assembled polymer films containing cyclodextrins[J]. Macromolecules, 2000, 33(26): 9471～9473.
[49] Arys X, Laschewsky A, Jonas A M. Ordered polyelectrolyte "multilayers" - 1. Mechanisms of growth and structure formation: A comparison with classical fuzzy "multilayers"[J]. Macromolecules, 2001, 34(10): 3318～3330.
[50] Laurent D, Schlenoff J B. Multilayer Assemblies of Redox Polyelectrolytes[J]. Langmuir, 1997, 13(6): 1552～1557.
[51] Hoogeveen N G, Cohen S M, Fleer G J, et al. Formation and Stability of Multilayers of Polyelectrolytes[J]. Langmuir, 1996, 12(15): 3675～3681.
[52] Lvov Y, Ariga K, Ichinose I, et al. Assembly of Multicomponent Protein Films by Means of Electrostatic Layer-by-Layer Adsorption[J]. Journal of theAmerican Chemical Society, 1995, 117(22): 6117～6123.
[53] Radtchenko I L, Sukhorukov G B, Leporatti S, et al. Assembly of Alternated Multivalent Ion/Polyelectrolyte Layers on Colloidal Particles. Stability of the Multilayers and Encapsulation of Macromolecules into Polyelectrolyte Capsules[J]. Journal of Colloid and Interface Science, 2000, 230(2): 272～280.
[54] Fou A C, Rubner M F. Molecular-level processing of conjugated polymers. 2. Layer-by-layer manipulation of in-situ polymerized p-type doped conducting polymers[J]. Macromolecules, 1995, 28(21): 7115～7120.
[55] Sukhishvili S A. Responsive polymer films and capsules via layer-by-layer assembly[J]. Current Opinion in Colloid and Interface Science, 2005, 10(1-2): 37～44.
[56] Lavalle P, Vivet V, Jessel N, et al. Direct evidence for vertical diffusion and exchange processes of polyanions and polycations in polyelectrolyte multilayer films[J]. Macromolecules, 2004, 37(3): 1159～1162.
[57] Lavalle P, Picart C, Mutterer J, et al. Modeling the Buildup of Polyelectrolyte Multilayer Films Having Exponential Growth[J]. Journal of Physical Chemistry B, 2004, 108(2): 635～648.
[58] Messina R. Polyelectrolyte multilayering on a charged planar surface[J]. Macromolecules, 2004, 37(2): 621～629.
[59] Poptoshev E, Schoeler B, Caruso F. Influence of solvent quality on the growth of polyelectrolyte multilayers[J]. Langmuir, 2004, 20(3): 829～834.
[60] Serizawa T, Goto H, Kishida T, et al. Improved alternate deposition of biodegradable naturally occurring polymers onto a quartz crystal microbalance[J]. Journal of Polymer Science, Part A: Polymer Chemistry, 1999, 37(6): 801～804.
[61] Hiller J A, Rubner M F. Reversible molecular memory and pH-switchable swelling transitions in polyelectrolyte multilayers[J]. Macromolecules, 2003, 36(11): 4078～4083.
[62] Yang S Y, Mendelsohn J D, Rubner M F. New class of ultrathin, highly cell-adhesion-resistant polyelectrolyte multilayers with micropatterningcapabilities[J]. Biomacromolecules, 2003, 4(4): 987～994.
[63] Yoshihiro I, Kazuhiko N, Eisaku L, et al. Fluorescence study of polyelectrolyte complex formation: 2. Effect of acidity of polyanions on complexation[J]. Polymer, 1992, 33(14): 3016～3023.
[64] Dubas S T, Schlenoff J B. Factors Controlling the Growth of Polyelectrolyte Multilayers[J]. Macromolecules, 1999, 32(24): 8153～8160.
[65] Salom, ki M, Vinokurov I A, et al. Effect of temperature on the buildup of polyelectrolyte multilayers[J]. Langmuir, 2005, 21(24): 11232～11240.
[66] Itoh Y, Matsusaki M, Kida T, et al. Enzyme-responsive release of encapsulated proteins from biodegradable hollow capsules[J]. Biomacromolecules, 2006, 7(10): 2715～2718.
[67] De G B, Dejugnat C, Verhoeven E, et al. Layer-by-layer coating of degradable microgels for pulsed drug delivery[J]. Journal of Controlled Release, 2006, 116(2 SPEC ISS): 159～169.
[68] Moya S E, Toca-Herrera J L. From hollow shells to artificial cells: Biointerface engineering on polyelectrolyte capsules[J]. Journal of Nanoscience and Nanotechnology, 2006, 6(8): 2329～2337.
[69] DeLongchamp D M, Kastantin M, Hammond P T. High-contrast electrochromism from layer-by-layer polymer films[J]. Chemistry of Materials, 2003, 15(8): 1575～1586.
[70] Cho J, Char K, Young K D. Change in the quantum efficiency due to relative thickness variation of hole transport and emitting layers in a self-assembled device[J]. Thin Solid Films, 2002, 415(1-2): 303～307.
[71] Han S, Briseno A L, Shi X, et al. Polyelectrolyte-coated nanosphere lithographic patterning of surfaces: Fabrication and characterization of electropolymerized thin polyaniline honeycomb films[J]. Journal of Physical Chemistry B, 2002, 106(25): 6465～6472.
[72] Dayang W, Caruso R A, Caruso F. Synthesis of macroporous titania and inorganic composite materials from coated colloidal spheres-a novel route to tunepore morphology[J]. Chemistry of Materials, 2001, 13(2): 364～371.
[73] Tieke B, Toutianoush A, Jin W. Selective transport of ions and molecules across layer-by-layer assembled membranes of polyelectrolytes, p-sulfonato-calix[n]arenes and Prussian Blue-type complex salts[J]. Advances in Colloid and Interface Science, 2005, 116(1-3): 121～131.
[74] Caruso F, Donath E, Moehwald H. Influence of polyelectrolyte multilayer coatings on Foerster resonance energy transfer between 6-carboxyfluorescein and rhodamine B-labeled particles in aqueous solution[J]. Journal of Physical Chemistry B, 1998, 102(11): 2011～2016.
[75] Donath E, Walther D, Shilov V N, et al. Nonlinear hairy layer theory of electrophoretic fingerprinting applied to consecutive layer by layer polyelectrolyte adsorption onto charged polystyrene latex particles[J]. Langmuir, 1997, 13(20): 5294～5305.
[76] Johnston A P, Cortez C, Angelatos A S, et al. Layer-by-layer engineered capsules and their applications[J]. Current Opinion in Colloid and Interface Science, 2006, 11(4): 203～209.
[77] Donath E, Sukhorukov G B, Caruso F, et al. Novel Hollow Polymer Shells by Colloid-Templated Assembly of Polyelectrolytes[J]. Angewandte Chemie International Edition, 1998, 37(16): 2201～2205.
[78] Caruso R A, Susha A, Caruso F. Multilayered Titania, Silica, and Laponite Nanoparticle Coatings on Polystyrene Colloidal Templates and Resulting Inorganic Hollow Spheres[J]. Chemistry of Materials, 2001, 13(2): 400～409.
[79] Changyou G S. Melamine Formaldehyde Core Decomposition as the Key Step Controlling Capsule Integrity: Optimizing the Polyelectrolyte Capsule Fabrication[J]. Macromolecular Chemistry and Physics, 2002, 203(7): 953～960.
[80] Gao C, Mohwald H, Shen J. Soluble microcapsules assembled stepwise from weak polyelectrolytes using acid-decomposable cores[J]. Advanced Materials, 2003, 15(11): 930～933.
[81] Tong W, Gao C. Multilayer microcapsules with tailored structures forbio-related applications[J]. Journal of Materials Chemistry, 2008, 18(32): 3799～3812.
[82] Sukhorukov G B, Donath E, Davis S, et al. Stepwise polyelectrolyte assembly on particle surfaces: a novel approach to colloid design[J]. Polymers for Advanced Technologies, 1998, 9(10-11): 759～767.
[83] Zhu Y, Gao C, He T, et al. Layer-by-layer assembly to modify poly(L-lactic acid) surface toward improving its cytocompatibility to human endothelial cells[J]. Biomacromolecules, 2003, 4(2): 446～452.
[84] Itoh Y, Matsusaki M, Kida T, et al. Enzyme-responsive release of encapsulated proteins from biodegradable hollow capsules[J]. Biomacromolecules, 2006, 7(10): 2715～2718.
[85] Zhu Y, Shi J, Shen W, et al. Stimuli-responsive controlled drug release from a hollow mesoporous silica sphere/polyelectrolyte multilayer core-shell structure[J]. Angewandte Chemie - International Edition, 2005, 44(32): 5083～5087.
[86] Han B, Shen B, Wang Z, et al. Layered microcapsules for daunorubicin loading and release as well as in vitro and in vivo studies[J]. Polymers for Advanced Technologies, 2008, 19(1): 36～46.
[87] Leporatti S, Gao C, Voigt A, et al. Shrinking of ultrathin polyelectrolyte multilayer capsules upon annealing: A confocal laser scanning microscopy and scanning force microscopy study[J]. European Physical Journal E, 2001, 5(1): 13～20.
[88] Leporatti S, Voigt A, Mitl, et al. Scanning force microscopy investigation of polyelectrolyte nano- and microcapsule wall texture[J]. Langmuir, 2000, 16(9): 4059～4063.
[89] Gao C, Leporatti S, Donath E, et al. Surface texture of poly(styrenesulfonate sodium salt) and poly(diallyldimethylammonium chloride) micron-sized multilayer capsules: A scanning force and confocal microscopy study[J]. Journal of Physical Chemistry B, 2000, 104(30): 7144～7149.
[90] Qiu X, Leporatti S, Donath E, et al. Studies on the drug release properties of polysaccharide multilayers encapsulated ibuprofen microparticles[J]. Langmuir,2001, 17(17): 5375～5380.
[91] Balabushevitch N G, Sukhorukov G B, Moroz N A, et al. Encapsulation of proteins by layer-by-layer adsorption of polyelectrolytes onto protein aggregates: Factors regulating the protein release[J]. Biotechnology and Bioengineering, 2001, 76(3): 207～213.
[92] Caruso F, Trau D, Moehwald H, et al. Enzyme encapsulation in layer-by-layer engineered polymer multilayer capsules[J]. Langmuir, 2000, 16(4): 1485～1488.
[93] Cao C, Liu X, Shen J, et al. Spontaneous deposition of horseradish peroxidase into polyelectrolyte multilayer capsules to improve its activity and stability[J]. Chemical Communication, 2002, (17): 1928～1929.
[94] Dahne L, Leporatti S, Donath E, et al. Fabrication of micro reaction cages with tailored properties[J]. Journal of the American Chemical Society, 2001, 123(23): 5431～5436.
[95] Gaponik N, Radtchenko I L, Sukhorukov G B, et al. Toward encoding combinatorial libraries: Charge-driven microencapsulation of semiconductor nanocrystals luminescing in the visible and near IR[J]. Advanced Materials, 2002, 14(12): 879～882.
[96] Chuang C Y, Don T M, Chiu W Y. Synthesis and properties of chitosan-modified poly(acrylic acid)[J]. Journal of Applied Polymer Science, 2008, 109(5): 3382～3389.
[97] Hajdu I, Bodnar M, Filipcsei G, et al. Nanoparticles prepared by self-assembly of Chitosan and poly-γ-glutamic acid[J]. Colloid and Polymer Science, 2008, 286(3): 343～350.
[98] Tian Y, Bromberg L, Lin S N, et al. Complexation and release of doxorubicin from its complexes with pluronic P85-b-poly(acrylic acid) block copolymers[J]. Journal of Controlled Release, 2007, 121(3): 137～145.
[99] Veronese F M, Morpurgo M. Bioconjugation in pharmaceutical chemistry[J]. II Farmaco, 1999, 54(8): 497～516.
[100] Miyata K, Kakizawa Y, Nishiyama N, et al. Freeze-dried formulations for in vivo gene delivery of PEGylated polyplex micelles with disulfide crosslinked coresto the liver[J]. Journal of Controlled Release, 2005, 109(1-3): 15～23.
[101] Fwu-Long M S. Chitosan-Polyelectrolyte complexation for the preparation of gel beads and controlled release of anticancer drug. I. Effect of phosphorous polyelectrolyte complex and enzymatic hydrolysis of polymer[J]. Journal of Applied Polymer Science, 1999, 74(7): 1868～1879.
[102] Fwu-Long M S. Chitosan-polyelectrolyte complexation for the preparation of gel beads and controlled release of anticancer drug. II. Effect of pH-dependent ionic crosslinking or interpolymer complex using tripolyphosphate or polyphosphate as reagent[J]. Journal of Applied Polymer Science, 1999, 74(5): 1093～1107.
[103] Haidar Z S, Hamdy R C, Tabrizian M. Protein release kinetics for core-shell hybrid nanoparticles based on the layer-by-layer assembly of alginate and chitosan on liposomes[J]. Biomaterials, 2008, 29(9): 1207～1215.
[104] Li C. Poly(L-glutamic acid)–anticancer drug conjugates[J]. Advanced Drug Delivery Reviews, 2002, 54(5): 695～713.
[105] Peniche C, Arguelles-Monal W, Peniche H, et al. Chitosan: An Attractive Biocompatible Polymer for Microencapsulation[J]. Macromolecular Bioscience, 2003, 3(10): 511～520.
[106]曹田,尹静波,罗坤,等.高分子量的聚L-谷氨酸的合成与表征[J].高等学校化学学报, 2006, 27(2): 369～371.
[107]谢勇涛,尹静波,赵长稳,等.聚谷氨酸苄酯脱保护制备聚L-谷氨酸的正交实验研究[J].高等学校化学学报, 2008, 29(1): 197～200.
[108] Lavasanifar A, Samuel J, Kwon G S. Poly(ethylene oxide)-block-poly(-amino acid) micelles for drug delivery[J]. Advanced Drug Delivery Reviews, 2002, 54(2): 169～190.
[109]张国林,吴秋华,潘彤, et al. AB型两亲聚L-谷氨酸-苄酯-聚乙二醇嵌段共聚物的合成与表征[J].高分子学报, 2004, (2): 223～227.
[110]王琴梅,潘仕荣,等.聚谷氨酸苄酯—聚乙二醇嵌段共聚物的合成和表征[J].功能高分子学报, 2001, 14(1): 61～65.
[111] Deng M, Wang R, Rong G, et al. Synthesis of a novel structural triblockcopolymer of poly(γ-benzyl-L-glutamic acid)-b-poly(ethylene oxide)-b-poly(ε-caprolactone)[J]. Biomaterials, 2004, 25(17): 3553～3558.
[112] Guan H, Xie Z, Zhang P, et al. Synthesis and Characterization of Biodegradable Amphiphilic Triblock Copolymers Containing L-Glutamic Acid Units[J]. Biomacromolecules, 2005, 6(4): 1954～1960.
[113] Wang L Y, Wang S G, Bei J Z. Synthesis and characterization of macroinitiator-amino terminated PEG and poly(γ-benzyl-L-glutamate)-PEO-poly(γ-benzyl-L-glutamate triblock copolymer[J]. Polymers for Advanced Technologies, 2004, 15(10): 617～621.
[114] Deng C, Rong G, Tian H, et al. Synthesis and characterization of poly(ethylene glycol)-b-poly (L-lactide)-b-poly(L-glutamic acid) triblock copolymer[J]. Polymer, 2005, 46(3): 653～659.
[115] Deng C, Tian H, Zhang P, et al. Synthesis and Characterization of RGD Peptide Grafted Poly(ethylene glycol)-b-Poly(L-lactide)-b-Poly(L-glutamic acid) Triblock Copolymer[J]. Biomacromolecules, 2006, 7(2): 590～596.
[116] Matralis A, Sotiropoulou M, Bokias G, et al. Water-soluble stoichiometric polyelectrolyte complexes based on cationic comb-type copolymers[J]. Macromolecular Chemistry and Physics, 2006, 207(12): 1018～1025.
[117]项茂良,江明.多组分聚合物体系中的相容和络合[J].高分子通报, 1997, (1): 15～21.
[118]陈俊燕,项茂良,江明.由特殊相互作用导致的高分子间的络合Ⅸ.聚(苯乙烯-co-4-乙烯基苯酚)/聚(苯乙烯-co-4-乙烯基吡啶)在本体中的相容-络合行为[J].高分子学报, 1999, (5): 545～550.
[119] de Vasconcelos C L, Bezerril P M, dos Santos D, et al. Effect of Molecular Weight and Ionic Strength on the Formation of Polyelectrolyte Complexes Based on Poly(methacrylic acid) and Chitosan[J]. Biomacromolecules, 2006, 7(4): 1245～1252.
[120] Ward C M, Fisher K D, Seymour L W. Turbidometric analysis of polyelectrolyte complexes formed between poly(L-lysine) and DNA[J]. Colloidsand Surfaces B: Biointerfaces, 1999, 16(1): 253～260.
[121] Hartlig S M, Carlesso G, Davidson J M, et al. Development of improve nanoparticle polyelectrolyte complex physicochemistry by nonstoichiometric mixing of polyions with similar molecular weights[J]. Biomacromolecules, 2007, 8(1): 265～272.
[122] Katayose S, Kataoka K. Water-Soluble Polyion Complex Associates of DNA and Poly(ethylene glycol)-Poly(L-lysine) Block Copolymer[J]. Bioconjugate Chemistry, 1997, 8(5): 702～707.
[123] Bronich T K, Kabanov A V. Soluble Complexes from Poly(ethylene oxide)-block-polymethacrylate Anions and N-Alkylpyridinium Cations[J]. Macromolecules, 1997, 30(12): 3519～3525.
[124] Schwarz S, Jaeger W, Bratskaya S, et al. Formation of polyelectrolyte complexes in a polycarboxybetaine/weak polyanion system[J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2006, 276(1-3): 65～71.
[125] Harada A, Kataoka K. Formation of Polyion Complex Micelles in an Aqueous Milieu from a Pair of Oppositely-Charged Block Copolymers with Poly(ethylene glycol) Segments[J]. Macromolecules, 1995, 28(15): 5294～5299.
[126] Gohy J F, Varshney S K, Jerome R. Water-Soluble Complexes Formed by Poly(2-vinylpyridinium)-block-poly(ethylene oxide) and Poly(sodium methacrylate)-block-poly(ethylene oxide) Copolymers[J]. Macromolecules, 2001, 34(10): 3361～3366.
[127] Chelushkin P S, Lysenko E A, Bronich T K, et al. Polyion complex nanomaterials from block polyelectrolyte micelles and linear polyelectrolytes of opposite charge: 1. Solution behavior[J]. Journal of Physical Chemistry B, 2007, 111(29): 8419～8425.
[128] Hofs B, De K A, Stuart M A. On the stability of (highly aggregated) polyelectrolyte complexes containing a charged-block-neutral diblock copolymer[J]. Journal of Physical Chemistry B, 2007, 111(20): 5621～5627.
[129] Kabanov A V, Bronich T K, Kabanov V A, et al. Soluble Stoichiometric Complexes from Poly(N-ethyl-4-vinylpyridinium) Cations and Poly(ethyleneoxide)-block-polymethacrylate Anions[J]. Macromolecules, 1996, 29(21): 6797～6802.
[130] Vinogradov S V, Bronich T K, Kabanov A V. Self-Assembly of Polyamine-Poly(ethylene glycol) Copolymers with Phosphorothioate Oligonucleotides[J]. Bioconjugate Chemistry, 1998, 9(6): 805～812.
[131] Harada A, Kataoka K. Chain length recognition: core-shell supramolecular assembly from oppositely charged block copolymers[J]. Science, 1999, 283(5398): 65～67.
[132] Kabanov A V, Bronich T K, Kabanov V A, et al. Soluble Stoichiometric Complexes from Poly(N-ethyl-4-vinylpyridinium) Cations and Poly(ethylene oxide)-block-polymethacrylate Anions[J]. Macromolecules, 1996, 29(21): 6797～6802.
[133] Kondo T, Sawatari C, Manley R S, et al. Characterization of hydrogen bonding in cellulose-synthetic polymer blend systems with regioselectively substituted methylcellulose[J]. Macromolecules, 1994, 27(1): 210～215.
[134] Kolhe P, Kannan R M. Improvement in ductility of chitosan through blending and copolymerization with PEG: FTIR investigation of molecular interactions[J]. Biomacromolecules, 2003, 4(1): 173～180.
[135] Zeng M, Fang Z, Xu C. Effect of compatibility on the structure of the microporous membrane prepared by selective dissolution of chitosan/synthetic polymer blend membrane[J]. Journal of Membrane Science, 2004, 230(1-2): 175～181.
[136] Luo K, Yin J, Song Z, et al. Biodegradable Interpolyelectrolyte Complexes Based on Methoxy Poly(ethylene glycol)-b-poly(α,l-glutamic acid) and Chitosan[J]. Biomacromolecules, 2008, 9(10): 2653～2661.
[137] Rosca C, Popa M I, Lisa G, et al. Interaction of chitosan with natural or synthetic anionic polyelectrolytes. 1. The chitosan-carboxymethylcellulose complex[J]. Carbohydrate Polymers, 2005, 62(1): 35～41.
[138] Fan L, Du Y, Zhang B, et al. Preparation and properties of alginate/carboxymethyl chitosan blend fibers[J]. Carbohydrate Polymers, 2006,65(4): 447～452.
[139] Luo K, Yin J, Khutoryanskaya O V, et al. Mucoadhesive and Elastic Films Based on Blends of Chitosan and Hydroxyethylcellulose[J]. Macromolecular Bioscience, 2008, 8(2): 184～192.
[140] He Y, Zhu B, Inoue Y. Hydrogen bonds in polymer blends[J]. Progress in Polymer Science, 2004, 29(10): 1021～1051.
[141] Lau C, Mi Y. A study of blending and complexation of poly(acrylic acid)/poly(vinyl pyrrolidone)[J]. Polymer, 2002, 43(3): 823～829.
[142] Huglin M B, Rego J M, Gooda S R. Comments on thermal transitions in some polyelectrolyte complexes[J]. Macromolecules, 1990, 23(26): 5359～5361.
[143] Huglin M B, Webster L, Robb I D. Complex formation between poly(4-vinylpyridinium chloride) and poly[sodium(2-acrylamido-2-methyl propane sulfonate)] in dilute aqueous solution[J]. Polymer, 1996, 37(7): 1211～1215.
[144] Smitha B, Sridhar S, Khan A A. Polyelectrolyte complexes of chitosan and poly(acrylic acid) as proton exchange membranes for fuel cells[J]. Macromolecules, 2004, 37(6): 2233～2239.
[145] Fang L, Goh S H. Miscible chitosan/tertiary amide polymer blends[J]. Journal of Applied Polymer Science, 2000, 76(12): 1785～1790.
[146] Lee S J, Kim S S, Lee Y M. Interpenetrating polymer network hydrogels based on poly(ethylene glycol) macromer and chitosan[J]. Carbohydrate Polymers, 2000, 41(2): 197～205.
[147] Yang J, Zhao T, Cui J, et al. Nonisothermal crystallization behavior of the poly(ethylene glycol) block in poly(L-lactide)poly(ethylene glycol) diblock copolymers: Effect of the poly(L-lactide) block length[J]. Journal of Polymer Science, Part B: Polymer Physics, 2006, 44(22): 3215～3226.
[148] Huang C I, Tsai S H, Chen C M. Isothermal crystallization behavior of poly(L-lactide) in poly(L-lactide)-block-poly(ethylene glycol) diblock copolymers[J]. Journal of Polymer Science, Part B: Polymer Physics, 2006, 44(17): 2438～2448.
[149] Rambo B M, Lavigne J J. Defining self-assembling linearoligo(dioxaborole)s[J]. Chemistry of Materials, 2007, 19(15): 3732～3739.
[150] Wang Y, Angelatos A S, Caruso F. Template synthesis of nanostructured materials via layer-by-layer assembly[J]. Chemistry of Materials, 2008, 20(3): 848～858.
[151] Stockton W B, Rubner M F. Molecular-Level Processing of Conjugated Polymers. 4. Layer-by-Layer Manipulation of Polyaniline via Hydrogen-Bonding Interactions[J]. Macromolecules, 1997, 30(9): 2717.
[152] Richert L, Lavalle P, Payan E, et al. Layer by Layer Buildup of Polysaccharide Films: Physical Chemistry and Cellular Adhesion Aspects[J]. Langmuir, 2004, 20(2): 448～458.
[153] Lavalle P, Gergely C, Cuisinier F J, et al. Comparison of the structure of polyelectrolyte multilayer films exhibiting a linear and an exponential growth regime: An in situ atomic force microscopy study[J]. Macromolecules, 2002, 35(11): 4458～4465.
[154]余海湖.静电自组装纳米复合薄膜研究[博士].武汉:武汉理工大学, 2002.
[155]李家值.半导体化学原理[M].北京:科学出版社, 1980.
[156] Li Q L, Chen Z Q, Darvell B W, et al. Chitosan-phosphorylated chitosan polyelectrolyte complex hydrogel as an osteoblast carrier[J]. Journal of Biomedical Materials Research - Part B Applied Biomaterials, 2007, 82(2): 481～486.
[157] Boulmedais F, Frisch B, Etienne O, et al. Polyelectrolyte multilayer films with pegylated polypeptides as a new type of anti-microbial protection for biomaterials[J]. Biomaterials, 2004, 25(11): 2003～2011.
[158] Picart C, Lavalle P, Hubert P, et al. Buildup mechanism for poly(L-lysine)/hyaluronic acid films onto a solid surface[J]. Langmuir, 2001, 17(23): 7414～7424.
[159] Elbert D L, Herbert C B, Hubbell J A. Thin polymer layers formed by polyelectrolyte multilayer techniques on biological surfaces[J]. Langmuir, 1999, 15(16): 5355～5362.
[160] Ruths J, Essler F, Decher G, et al. Polyelectrolytes. I: Polyanion/polycationmultilayers at the air/monolayer/water interface as elements for quantitative polymer adsorption studies and preparation of hetero-superlattices on solid surfaces[J]. Langmuir, 2000, 16(23): 8871～8878.
[161] Ladam G, Schaad P, Voegel J C, et al. In situ determination of the structural properties of initially deposited polyelectrolyte multilayers[J]. Langmuir, 2000, 16(3): 1249～1255.
[162] Lavalle P, Gergely C, Cuisinier F J, et al. Comparison of the structure of polyelectrolyte multilayer films exhibiting a linear and an exponential growth regime: An in situ atomic force microscopy study[J]. Macromolecules, 2002, 35(11): 4458～4465.
[163] Miyashita N, M, hwald H, et al. 2D structure of unsaturated fatty acid amide mono- and multilayer on graphite: Self-assembly and thermal behavior[J]. Chemistry of Materials, 2007, 19(17): 4259～4262.
[164] Yoo D, Shiratori S S, Rubner M F. Controlling Bilayer Composition and Surface Wettability of Sequentially Adsorbed Multilayers of Weak Polyelectrolytes[J]. Macromolecules, 1998, 31(13): 4309～4318.
[165] Shiratori S S, Rubner M F. pH-dependent thickness behavior of sequentially adsorbed layers of weak polyelectrolytes[J]. Macromolecules, 2000, 33(11): 4213～4219.
[166] Wang X, Kim H J, Xu P, et al. Biomaterial coatings by stepwise deposition of silk fibroin[J]. Langmuir, 2005, 21(24): 11335～11341.
[167] Flexer V, Forzani E S, Calvo E J, et al. Structure and thickness dependence of "molecular wiring" in nanostructured enzyme multilayers[J]. Analytical Chemistry, 2006, 78(2): 399～407.
[168] Ulbrich K, Subr V. Polymeric anticancer drugs with pH-controlled activation[J]. Advanced Drug Delivery Reviews, 2004, 56(7): 1023～1050.
[169] Zhu L, Ma J, Jia N, et al. Chitosan-coated magnetic nanoparticles as carriers of 5-Fluorouracil: Preparation, characterization and cytotoxicity studies[J]. Colloids and Surfaces B: Biointerfaces, 2009, 68(1): 1～6.
[170]郑爱萍,刘海宏,李宏斌,等. 5-氟脲嘧啶壳聚糖微球的制备及体外释放特性[J].中国药科大学学报, 2004, 35(4): 318～323.
[171]李可欣,陈大为,赵秀丽,等.分散-交联法制备氟尿嘧啶壳聚糖微球的研究[J].中国药学杂志, 2005, 40(18): 1392～1395.
[172]王怀玉,董利民,昝青峰,等.乳化交联法制备壳聚糖微球粘连原因分析[J].功能材料, 2007, 38(A05): 1923～1925.
[173] Schoeler B, Kumaraswamy G, Caruso F. Investigation of the influence of polyelectrolyte charge density on the growth of multilayer thin films prepared by the layer-by-layer technique[J]. Macromolecules, 2002, 35(3): 889～897.
[174] Milkova V, Radeva T. Effect of chain length and charge density on the construction of polyelectrolyte multilayers on colloidal particles[J]. Journal of Colloid and Interface Science, 2007, 308(2): 300～308.
[175] Grigoriev D O, Bukreeva T, Mohwald H, et al. New Method for Fabrication of Loaded Micro- and Nanocontainers: Emulsion Encapsulation by Polyelectrolyte Layer-by-Layer Deposition on the Liquid Core[J]. Langmuir, 2008, 24(3): 999～1004.
[176] Zhao Q, Han B, Wang Z, et al. Hollow chitosan-alginate multilayer microcapsules as drug delivery vehicle: doxorubicin loading and in vitro and in vivo studies[J]. Nanomedicine: Nanotechnology, Biology, and Medicine, 2007, 3(1): 63～74.
[177]刘亚军,朱以华,张素秋,等.单分散三聚氰胺甲醛微球的制备[J].功能高分子学报, 2004, 17(1): 113～118.
[178] Al H, Gao J. Size-controlled polyelectrolyte nanocapsules via layer-by-layer self-assembly[J]. Journal of Materials Science, 2004, 39(4): 1429～1432.
[179] Gupta K C, Jabrail F H. Glutaraldehyde and glyoxal cross-linked chitosan microspheres for controlled delivery of centchroman[J]. Carbohydrate Research, 2006, 341(6): 744～756.