温度-pH敏聚合物脂质体的合成、结构、性质及相行为
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摘要
脂质体作为药物载体以来,敏感性脂质体引起了越来越多的学者的关注。在这些敏感性脂质体中,pH敏感性脂质体倍受关注的原因是癌变细胞周围的组织液的pH值要比人体正常细胞的pH值要低,人们可利用这个特性设计pH促使膜破裂和融合作用导致活性组分进入细胞质的系统。目前研究工作表明,聚合物能够使脂质体具有pH敏感,可改变脂质体膜的组成或者修饰膜的表面,并且可以延长脂质体在体内的循环时间和增加在细胞内的积累。另外,研究表明温敏脂质体可在相变温度控制释放药物。脂质体的相变温度可以通过聚合物的亲水或疏水组分来调变。目前,pH—温度双敏脂质体鲜见报道。pH—温度双敏脂质体的合成及性质,在空间上和时间上控制释放药物都非常重要,是一个具有挑战性的研究课题。
在本论文中,我们合成了具有pH—温度敏感共聚物和pH—温度敏感聚合物脂质体,研究了共聚物溶液和聚合物脂质体溶液的相行为,讨论了聚合物脂质体对药物的控制释放。得到主要结论如下：
1、可以通过调节共聚物的组成控制合成不同pH相变的共聚物。共聚物溶液的相行为受到共聚物组成和溶液浓度的影响,随着共聚物中亲水组分甲基丙烯酸(MAA)含量的增加,共聚物溶液的温度和pH敏感性增强,共聚物溶液的相变温度(LCST)和相变pH (pH*)降低。共聚物溶液在pH*时,有着较高的相变温度。共聚物溶液浓度影响共聚物的LCST,但不影响相变pH
2、共聚物的临界胶束浓度(CMC)与共聚物组成相关联,其疏水性越强,CMC越小。在固定共聚物丙烯酸十八酯(ODA)含量下,CMC随MAA含量的增加而增大。
3、当共聚物溶液的温度低于LCST时,共聚物胶束不受温度和pH的影响。温度高于LCST,共聚物胶束的粒径随着温度的升高而增大。在相变pH,共聚物胶束的平均粒径达到最小值。
4、聚合物脂质体的相变温度及粒径均受到共聚物以及盐酸小檗碱的影响,共聚物脂质体在相变pH时,脂质体的平均粒径和相变温度均为最大值。当共聚物与卵磷脂的质量比为1:2时,聚合物脂质体的相变温度和粒径都达到最大,聚合物脂质体最为稳定。盐酸小檗碱的加入,减小了聚合物脂质体的平均粒径,同时还降低了聚合物脂质体的相变温度,但是对相变pH没有影响。
5、当释放条件同时满足聚合物脂质体的相变温度及相变pH时,从聚合物脂质体中释放盐酸小檗碱可以达到最大。
Since liposome was proposed as a drug carrier, many attentions have been paid to design stimuli-sensitive liposome. Among these stimuli, pH-sensitive liposome has attracted many researchers' attentions. As the pH of endosoma of the cancerous cell is lower than that of extracellular fluids, this feature has been exploited in the design of systems that facilitate the delivery of active compounds to the cytoplasm via a pH-dependent membrane-disruptive and/or fusogenic action. Recent studies have demonstrated that polymers have also investigated to confer pH-responsiveness to liposome. The addition of polymers can alter the composition of membrane or modify the surface of liposome, and it can exhibit prolonged circulation times in vivo and accumulate in tumors. Temperature sensitive liposome has been investigated to control release drug at phase transition temperature in many-studies. The phase transition temperature of the liposome can be changed by changing the hydrophilic or hydrophobic monomers of the polymer. However, to the best of our knowledge, the report regarding pH-temperature sensitive copolymer-liposome is scarce. The studies of synthesis and property of pH-temperature sensitive copolymer-liposome are hence of most importance and remains a challenging problem, and the research focuses on controlled drug release both spatially and temporally.
In this thesis, we focused on synthesis of the pH-temperature sensitive copolymer and pH-temperature sensitive copolymer-liposome, the phase behaviors of the copolymer solution and copolymer-liposome solution, and the control drug release from the copolymer-liposome. The main results presented in this thesis are summarized below.
1. Copolymer with various phase transition pH can be synthesized by controlling composition of the copolymer. The phase transition of the copolymer depends on the composition and concentration of the copolymer. The temperature-pH sensitivity of the copolymer solution increases with the MAA content in the copolymer. The lower critical solution temperature (LCST) and phase transition pH (pH*) of the copolymer solution decrease with the increasing MAA content. The LCST of the copolymer solution can reach a maximum at the pH*. The LCST decreases with the increasing copolymer concentration, but the pH* was not affected by the concentration.
2. The critical micelle concentration (CMC) of the copolymer solution depends on the copolymer composition. The CMC decreases with increasing the hydrophobicity of the copolymer. The CMC increases with MAA content at the fixed ODA content.
3. The micelle of the copolymer was not affected by the temperature and pH, when the temperature was below the LCST of the copolymer solution. The mean diameter of the micelle increases with temperature, and it can reach the minimum at pH*.
4. The phase transition temperature and micelle size of the copolymer-liposome were affected by the copolymer and berberine hydrochloride (ber), and the mean diameter and phase transition temperature can reach the maximum at phase transition pH*. When the mass ration of the copolymer to SPC (w) was 1:2, the mean diameter and phase transition temperature was the maximum value. The copolymer-liposome was most stable at the pH* and w=1:2. The mean diameter and phase transition temperature were decreased by addition of berberine, but the pH* of the copolymer-liposome was not affected by addition of bererine.
5. The berberine release from the copolymer-liposome was the maximum value at the phase transition temperature and pH* of the copolymer-liposome.
在本论文中,我们合成了具有pH—温度敏感共聚物和pH—温度敏感聚合物脂质体,研究了共聚物溶液和聚合物脂质体溶液的相行为,讨论了聚合物脂质体对药物的控制释放。得到主要结论如下：
1、可以通过调节共聚物的组成控制合成不同pH相变的共聚物。共聚物溶液的相行为受到共聚物组成和溶液浓度的影响,随着共聚物中亲水组分甲基丙烯酸(MAA)含量的增加,共聚物溶液的温度和pH敏感性增强,共聚物溶液的相变温度(LCST)和相变pH (pH*)降低。共聚物溶液在pH*时,有着较高的相变温度。共聚物溶液浓度影响共聚物的LCST,但不影响相变pH
2、共聚物的临界胶束浓度(CMC)与共聚物组成相关联,其疏水性越强,CMC越小。在固定共聚物丙烯酸十八酯(ODA)含量下,CMC随MAA含量的增加而增大。
3、当共聚物溶液的温度低于LCST时,共聚物胶束不受温度和pH的影响。温度高于LCST,共聚物胶束的粒径随着温度的升高而增大。在相变pH,共聚物胶束的平均粒径达到最小值。
4、聚合物脂质体的相变温度及粒径均受到共聚物以及盐酸小檗碱的影响,共聚物脂质体在相变pH时,脂质体的平均粒径和相变温度均为最大值。当共聚物与卵磷脂的质量比为1:2时,聚合物脂质体的相变温度和粒径都达到最大,聚合物脂质体最为稳定。盐酸小檗碱的加入,减小了聚合物脂质体的平均粒径,同时还降低了聚合物脂质体的相变温度,但是对相变pH没有影响。
5、当释放条件同时满足聚合物脂质体的相变温度及相变pH时,从聚合物脂质体中释放盐酸小檗碱可以达到最大。
Since liposome was proposed as a drug carrier, many attentions have been paid to design stimuli-sensitive liposome. Among these stimuli, pH-sensitive liposome has attracted many researchers' attentions. As the pH of endosoma of the cancerous cell is lower than that of extracellular fluids, this feature has been exploited in the design of systems that facilitate the delivery of active compounds to the cytoplasm via a pH-dependent membrane-disruptive and/or fusogenic action. Recent studies have demonstrated that polymers have also investigated to confer pH-responsiveness to liposome. The addition of polymers can alter the composition of membrane or modify the surface of liposome, and it can exhibit prolonged circulation times in vivo and accumulate in tumors. Temperature sensitive liposome has been investigated to control release drug at phase transition temperature in many-studies. The phase transition temperature of the liposome can be changed by changing the hydrophilic or hydrophobic monomers of the polymer. However, to the best of our knowledge, the report regarding pH-temperature sensitive copolymer-liposome is scarce. The studies of synthesis and property of pH-temperature sensitive copolymer-liposome are hence of most importance and remains a challenging problem, and the research focuses on controlled drug release both spatially and temporally.
In this thesis, we focused on synthesis of the pH-temperature sensitive copolymer and pH-temperature sensitive copolymer-liposome, the phase behaviors of the copolymer solution and copolymer-liposome solution, and the control drug release from the copolymer-liposome. The main results presented in this thesis are summarized below.
1. Copolymer with various phase transition pH can be synthesized by controlling composition of the copolymer. The phase transition of the copolymer depends on the composition and concentration of the copolymer. The temperature-pH sensitivity of the copolymer solution increases with the MAA content in the copolymer. The lower critical solution temperature (LCST) and phase transition pH (pH*) of the copolymer solution decrease with the increasing MAA content. The LCST of the copolymer solution can reach a maximum at the pH*. The LCST decreases with the increasing copolymer concentration, but the pH* was not affected by the concentration.
2. The critical micelle concentration (CMC) of the copolymer solution depends on the copolymer composition. The CMC decreases with increasing the hydrophobicity of the copolymer. The CMC increases with MAA content at the fixed ODA content.
3. The micelle of the copolymer was not affected by the temperature and pH, when the temperature was below the LCST of the copolymer solution. The mean diameter of the micelle increases with temperature, and it can reach the minimum at pH*.
4. The phase transition temperature and micelle size of the copolymer-liposome were affected by the copolymer and berberine hydrochloride (ber), and the mean diameter and phase transition temperature can reach the maximum at phase transition pH*. When the mass ration of the copolymer to SPC (w) was 1:2, the mean diameter and phase transition temperature was the maximum value. The copolymer-liposome was most stable at the pH* and w=1:2. The mean diameter and phase transition temperature were decreased by addition of berberine, but the pH* of the copolymer-liposome was not affected by addition of bererine.
5. The berberine release from the copolymer-liposome was the maximum value at the phase transition temperature and pH* of the copolymer-liposome.
引文
[1]高重辉.高分子化学.中国石化出版社,1997年12月.
[2]陈智强.SMA树脂工艺过程的中试研究.合成树脂及塑料.2000,5:65-66
[3]姜忠民,黎华明.苯乙烯—马来酸酐无规共聚物合成研究.弹性体.1998,1(6-9):
[4]焦健,丁春黎.苯乙烯—马来酸酐无规共聚物的合成.吉林工学院学报：自然科学版.2001,3(22)：51-53
[5]单国荣,陈伟国.苯乙烯与N—苯基马来酰亚胺本体共聚合动力学.化学反应工程与工艺.1996,3(12)：225-231
[6]潘祖仁.高分子化学.化学工业出版社,1997年6月.
[7]惠远峰,张立东,徐崇利,包海峰.氟代丙烯酸酯/MAA共聚物合成工艺研究.化工新型材料.2010,5:103-105
[8]钱静.烯丙基聚乙醇一丙烯酸共聚物合成工艺及分散性能研究.中国建材科技.2011,2：64-67
[9]王国祥,肖永峰.丙烯酸与丙烯酰胺的反相悬浮共聚合的研究.石化技术.2010,3:1-4
[10]金关泰.高分子化学的理论和应用进展.中国石化出版社,1995年3月.
[11]赵明,王荣民,张慧芳,李宏洲.反相乳液聚合制备丙烯酰胺-二甲基二烯丙基氯化铵阳离子共聚物.甘肃高师学报.2010,2(15)：20-23
[12]赵群,倪沛红,常华.两亲性高分子乳化剂的苯乙烯乳液聚合研究.精细石油化工进展.2009,5：41-43
[13]虞志光.高聚物分子量及其分布的测定.上海科学技术出版社,1984年7月.
[14]郑昌仁.高聚物分子量及其分布.化学工业出版社,1986年7月.
[15]殷敬华,莫志深.现代高分子物理学 (上册).科学出版社,2001年.
[16]何平笙,杨海洋,朱平平,瞿保均.高分子物理实验.中国科技大学出版社,2002年.
[17]杨玉良,胡汉杰.高分子物理.化工出版社,2001年.
[18]Webber ST, Munk P, Tuzar Z. S. Netherlands:Kluwer Academic Publishers,1996.
[19]Zhang LF, Eisenberg A. Formation of crew-cut aggregates of various morphologies from amphiphilic block copolymers in solution. Polymers for advanced technologies.1998,9: 677-699
[20]Zhang LF, EIsenberg A. Multiple Morphologies of "Crew-Cut" Aggregates of Polystyrene-b-poly(acrylic acid) Block Copolymers Science.1995,23:1728-1731
[21]Zhang LF, Eisenberg A. Multiple Morphologies and Characteristics of "Crew-Cut" Micelle-like Aggregates of Polystyrene-b-poly(acrylic acid) Diblock Copolymers in Aqueous Solutions. J Am Chem Soc.1996,118:3168-3181
[22]Aoi K, Tsutsamiuchi K, Okada M. Glycopeptide Synthesis by an.alpha.-Amino Acid N-Carboxyanhydride (NCA) Method:Ring-Opening Polymerization of a Sugar-Substituted NCA. Macromolecules.1994,27:875-877
[23]Kobayashi K, Tsuchida A, Usui T, Akaike T. A New Type of Artificial Glycoconjugate Polymer:A Convenient Synthesis and Its Interaction with Lectins. Macromolecules.1997,30: 2016-2020
[24]梁玉增,李子臣,李福绵.两亲性含糖嵌段共聚物在水中分子聚集形态的转变.高等学校化学学报.1999,11：1820-1822
[25]徐祖顺,封麟先,易昌凤,陈永春,程时远.两亲聚合物溶液性质及其乳液聚合的研究进展.高分子材料科学与工程.1998,14:1-4
[26]崔正刚.溶液表面化学.无锡轻工业大学,2001年2月.
[27]崔正刚,殷福珊.微乳化技术及应用.中国轻工业出版社,1999年2月.
[28]胡志标,王永强,曾广鹏,张超,夏必来,洪昕林,张高勇.催化链转移聚合制备接枝型两亲共聚物及其溶液性质研究.化学学报.2007,23：2656-2662
[29]Jhaveri SB, Koylu D, Maschke D, Carter KR. Synthesis of Polymeric Core-Shell Particles Using Surface-Initiated Living Free-Radical Polymerization. Journal of Polymer Science:Part A:Polymer Chemistry.2007,45:1575-1584
[30]Motornov M, Roiter Y, Tokarev I, Minko S. Stimuli-responsive nanoparticles, nanogels and capsules for integrated multifunctional intelligent systems. Progress in Polymer Science.2010,35:174-211
[31]Carlsen A, Lecommandoux S. Self-assembly of polypeptide-based block copolymer amphiphiles. Current Opinion in Colloid & Interface Science.2009,14:329-339
[32]Riess G, Hurtrez G, Babadur P. Encyclopedia of polymer science. New York:Wiley, 1985.
[33]徐祖顺,易昌凤,程时远.聚甲基丙烯酸甲酯接枝聚氧乙烯共聚物溶液性质的研究.高分子学报.2000,6:701-706
[34]Wu Chi. A slmplemodelforthe structure of sphedcalmicroemulsion. Macromolecules. 1994,27:298-299
[35]Sikora A, Tuzar Z. Association of two-block copolymer polystyrene—block-(2-vinylpyridine)in toluene. Makromol Chem.1983,184:2049-2059
[36]Astafieva I, Zhong XF, Eisenberg A. Critical micellization phenomena in block polyelectrolyte solution. Macromolecules.1993,26:7339-7352
[37]Quintana JR, Villacampa M, Katime IA. Micellization of apolystyrene-b-poly(ethylene/propylene)block copo lymer in n-dodecane/1,4-dioxane mloxanc mixtures(2):Structure and dimensions of micelles. Macromolecules.1993:606-611
[38]Kwon GS, Kataoka K. Block copolymer micelles as long-criculating drug vehicles. Advanced Drug Delivery Reviews.1995,16:295-309
[39]Jones M-C, Leroux J-C. Polymeric micelles-a new generation of colloidal drug carriers European Journal of Pharmaceutics and Biopharmaceutics.1999,48:101-111
[40]Yokoyama M, Sugiyama T, Okano T, Sakurai Y, Naito M, Kataoka K. Analysis of micelle formation of an adriamycinconjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer by gel permeation chromatography. Pharm Res.1993,10:895-899
[41]Nishiyama N, Kataoka K. Preparation and characterization of size-controlled polymeric micelle containing cis-dichloro-diammineplatinum (II) in the core. Journal of Controlled Release.2001,74:83-94
[42]Zhang JX, Qiu LY, Jin Y, Zhu KJ. Controlled nanoparticles formation by self-assembly of novel amphiphilic polyphosphazenes with poly(N-isopropylacrylamide) and ethyl glycinate as side groups. Reactive & Functional Polymers.2006,66:1630-1640
[43]Ma X, Cui Y, Zhao X, Zheng S, Tang XZ. Different deswelling behavior of temperature-sensitive microgels of poly(N-isopropylacrylamide) crosslinked by polyethyleneglycol dimethacrylates. Journal of Colloid and Interface Science.2004,276: 53-59
[44]Li Z, Xiong D, Xu B, Wu C, An YL, Ma RJ, Shi LQ. Fabrication of an asymmetric hollow particle with a thermo-sensitive PNIPAM inside corona. Polymer.2009,50:825-831
[45]Nie T, Zhao Y, Xie Z, Wu C. Micellar formation of poly(caprolactone-block-ethylene oxide-block-caprolactone) and its enzymatic biodegradation in aqueous dispersion. Macromolecules.2003,36:8825-8829
[46]Allen C, Maysinger D, A, E. Nano-engineering block copolymer aggregates for drug delivery. Colloids and Surfaces B:Biointerfaces.1999,16:3-27
[47]Zhang L, Hu Jiang X. Camptothecin derivative-loaded poly(caprolactone-co-lactide)-b-PEG-b-poly(caprolactone-co-lactide)nanoparticles and their biodistribution in mice. Journal of Controlled Release.2004,96:135-148
[48]Mrkic J, Saunders BR. Microgel Particles as a Matrix for Polymerization:A Study of Poly(N-isopropylacrylamide)-Poly(N-methylpyrrole) Dispersions. Journal of Colloid and Interface Science.2000,222:75-82
[49]Tsitsilianis C, Sfika V. Heteroarm star-like micelles formed from polystyrene-block-poly(2-vinyl pyridine)-block-poly(-methyl methacrylate) ABC copolymers in toluene. Macromlo Rapid Commoun.2001,22:647-651
[50]Wang X, Winnik M, Manners I. Synthesis and solution selfassembly of coil-crystalline-coil polyferrocenylphosphineb-polyferrocenylsilane-b-polysiloxane triblock copolymers. Macromolecules.2002,35:9748-9755
[51]Alexandridis P, Holzwarth JF, Alan Hatton T. Micellization of poly(ethyleneoxide) poly(propylene oxide)-poly(ethylene oxide)triblock copolymers in aqueous solutions thermodynamics of copolymer association. Macromolecules.1994,27:2414-2425
[52]Chung JE, Yokoyama M, Aoyagi T. Effect of molecular architecture of hydrophobically modified poly(N-isopropylacrylamide) on the formation of thermoresponsive core-shell micellar's drug carriers. Controlled Release.1998,53:119-130
[53]Dowding PJ, Vincent B, Williams E. Preparation and Swelling Properties of Poly(NIPAM) "Minigel" Particles Prepared by Inverse Suspension Polymerization. Journal of Colloid and Interface Science.2000,221:268-272
[54]徐祖顺,陈中华,陈焕钦,封麟先.用粘度法研究PMMA-g-PEO在甲苯中微胶束的形成.华南理工大学学报.2000,9:114-119
[55]EB, J, Hvidt S, Brown W. Effectsofsalts on the micellization and gelation of a triblock copolymer studied by rhelogy and light scattering. Macromolecules.1997,30: 2355-2364
[56]Bahadur P, Pandya K, Almgen M. Effect of inorganic salts on the micellar behavior of ethylene oxide—propylene oxide block copolymer in aqueous solution. Colloids Polymer science.1993,271:657-667
[57]赵锦花,孙多先.两亲接枝共聚物PECA-g-PEG胶束的CMC及表面带电性.应用化学.2004,8：844-846
[58]赵国玺.表面活性剂物理化学.北京大学出版社,1991年.
[59]K.霍姆博格,琼森B,科隆博格 B,林德曼B.水溶液中的表面活性剂和聚合物(原著第二版).化学工业出版社,200年3月.
[60]Rosen MJ. Surfactans and Interfacial Phenomena. Wiley Interscience, New York, 1989.
[61]La SB, Okano T, Kataoka K. Preparation and characterization of the micelle-forming polymeric drug indomethacinincorporated poly(ethylene oxide)-poly(betabenzyl 1-aspartate) block copolymer micelles. J Pharm Sci.1996,85:85-90
[62]Kabanov AV, Batrakova EV, Alakhov VY. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release.2002,82:189-212
[63]施斌,方超,裴元英.两亲性嵌段共聚物胶束的研究进展.中国医药工业杂志.2005,36：239-243
[64]Capek I. Fate of excited probes in micellar systems. Advanced Colloied Interface Science.2002,97:91-149
[65]徐金军,倪忠斌,陈明清PMMA-g-PEG的制备及其相转变性能研究.化工新型材料 2008,8:51-53
[66]胡吉,周光宇,陈彦模,朱美芳.相变调温PFT-PEG嵌段共聚物的性能和结构的 研究.东华大学学报.2006,3：105-109
[67]曾钫,刘新星.NIPA/DMAA共聚物及其水溶液相转变温度的研究.高分子材料科学与工程.1997,5:100-103
[68]Caillol S, Lecommandoux S, Mingotaud A.-F, Schappacher M, Soum A, Bryson N, Meyrueix R. Synthesis and self-assembly properties of peptide-polylactide block copolymers. Macromolecules.2003,36:1118-1124
[69]Qiu XY, Wang CQ, Shen J, Jiang MW. Controlled synthesis of amphiphilic rod-coil biodegradable maltoheptaose-graft-poly(-caprolactone) copolymers. Carbobydrate Polymers. 2011,83:1723-1729
[70]Guohua Chen, Allan S. Hoffman. Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH. Nature.1995,373:49-52
[71]Kiler J, Scranton AB, Peppas NA. Self-associating networks of poly(methacrylic acid-g-ethylene glycol). Macromolecules.1990,23:4944-4949
[72]李芳,刘守信,刘侠,张朝阳,余娟,房喻.温度/pH双敏感性接枝共聚物P(MAA-g-NIPAM)相行为研究.陕西师范大学学报.2007,3：52-56
[73]余娟丽,李守信,房喻,高改玲,王明珍.温度/pH敏感性P(MAA-g-DEAM)共聚物水溶液的相行为.物理化学学报.2006,22:579-583
[74]徐华,宋涛.磁性药物靶向治疗的发展.国外医学生物医学工程分册.2004,27:61-64
[75]贾利军,王德,余国芬,张怀武.磁性药物载体的合成.材料导报.2004,18:66-71
[76]Jodan A, Wuat P, Scholz R. Effects of magnetic fluid hyperthermia (MFH) on C3H mamary carcinoma in vivo. Int J Hyperthermia.1997,13:587
[77]张阳德,龚连生.磁性阿霉素白蛋白纳米粒的研制.中国现代医学杂志.2001,3:1-3
[78]王尊元,马臻.高分子及高分子药物在现代医药上的应用.浙江省医学科学院学报.1998,6：45-47
[79]纳榕,张强华.高分子载体在药物控释体系中的应用.淮阴工学院学报.2004,13:81-83
[80]李玲.纳米药物载体的研究.材料导报.2002,16:58-59
[81]罗毅,卓仁禧,范昌烈.短肽5-氟尿嘧啶前体药物的合成及其抗肿瘤活性研究.高等学校化学学报.1994,15：545-547
[82]Chelvi PT. Heat-mediated selective delivery of Liposome-associated melphalam in murine melanoma. Melanona Res.1995,5:321-326
[83]李立新,樊品,王学谦.脂质体包裹人血红蛋白微囊的制备及其对大鼠血液的影响.天津医药.2004,32：p101-103
[84]纪俊敏,谢文磊.脂质体作为药物载体的研究进展.郑州工程学院学报.2002,23: 68-72
[85]冯杨,马玉坤,周华晨,瞿光喜.新型脂质体的研究与应用.山东医药.2004,44:59-60
[86]肖超,吴新荣.紫杉醇磁性脂质体的制备与抗肿瘤作用研究.医药导报.2010,11：1401-1404
[87]周伟华,郭讯枝,张阳德,何剪太,曾昭武,刘星言,谭斐,赵劲风,潘一峰.纳米司莫司汀磁性脂质体的制备及表征.科技通报.2008,3:406-410
[88]黄义昆.脂质体作为药物载体研究进展.中国药师.2005,8:549-550
[89]郜海涛,顾黎,张鹏英,孔蕴,陈靠山,王鹏.牛蒡寡糖脂质体的制备和性质鉴定.科技通报.2010,6:863-868
[90]张方宇,何松.乳糖脂修饰苦参碱脂质体的肝靶向性和体外抑瘤作用研究.重庆医科大学学报.2009,6:747-751
[91]景恒翠,王国生,于阳.肺靶向穿心莲内酯脂质体的制备及体外释放特征.亚太传统医药.2010,8:41-42
[92]傅刘鹏,徐俊,黄思超,邱胜红,蔡绍晖.叶酸脂质体对乳腺癌4T1细胞的体内靶向性研究.山东医药.2010,7:23-25
[93]张丙杰,迟令懿,李永刚,祝侠丽,李牧,张娜,滕良珠,朱树干.热敏脂质体洛莫司汀热靶向化疗的实验研究.中华物理医学与康复杂志.2007,5:316-317
[94]董兰凤,赵兴茹,冯凤莲,范美菊,杨丽.阿霉素长循环热敏脂质体的研制及其靶向治疗肿瘤作用的研究.中国肿瘤生物治疗杂志.2005,1:52-56
[95]Wen SY, wang XH, Lin L, Guan W, Wang SQ. Preparation and property analysis of a hepatocyte targeting pH-sensitive liposome. World Journal of Gastroenterology.2004,2: 244-249
[96]王弘,王升启.反义寡核苷酸pH敏前体脂质体的制备及性质分析.生物化学与生物物理进展.2000,2:178-181
[97]曹宁宁,羡非,刘鹏.脂质体的制备方法及研究进展.天津理工学院学报.2003,19：30-35
[98]温演庆,杨斌,钱志勇.光敏纳米脂质体制备及其特性研究.中国医学工程.2008,2：84-85
[99]袁有成,易学瑞,祖萍,张宜俊.新型佐剂及其与重组HBsAg结合物的理化性质的研究.中国生物制品学杂志.2003,3：168-171
[100]李津明,张彦卓,朱宇,任君刚,李鑫.依托泊苷隐形脂质体的制备及其质量评价.中国医药工业杂志.2008,39:834-837
[101]汪多仁.卵膦脂脂质体开发与应用进展.化工中间体.2003,10:23-26
[102]张晶,杨静,吴基良,张琳.异甘草素脂质体的制备及稳定性考察.25.2005:1046-1048
[103]段逸松,于波涛,张志荣.米托蒽醌长循环脂质体的制备及药代动力学的研究.药学学报.2002,37:465-468
[104]夏书芹,许时婴.吐温80增溶-紫外分光光度法测定辅酶Q10脂质体的载量及包封率.食品与发酵工业.2005,10:131-135
[105]Frederiken L, Anton K, Hoogevest PV. Preparation of liposomes encapsulating water soluble compounds using supercritical carbon dioxide. J Pharm Sci.1997,86:921
[106]严宾,安学勤,白晶,张英华.超临界CO2法制备头孢唑啉钠脂质体.物理化学学报.2006,22：226-229
[107]文震,刘波,李琼,郑宗坤,游新奎,蒲一涛.超临界C02快速膨胀制备鱼腥草挥发油脂质体.过程工程学报.2009,9:350-354
[108]Simoes S, Moreira NJ, Fonseca C, Duzgunes N, Maria C, Lima PD. On the formulation of pH-sensitive liposomes with long circulation times. Advanced Drug Delivery Reviews.2004,56:947-965
[109]戈升荣,裴元英.pH敏感型脂质体释药机制研究概况.中国医药工业杂志.1998,29：564-568
[110]Hafez MI, Cullis PR. Roles of lipid polymorphism in intracellular delivery. Advanced Drug Delivery Reviews.2001,47:139-148
[111]Ellens H, Bentz J, Szoka FC. pH-induced destabilization of phosphatidylethanolamine-containing liposomes:Role of bilayer contact. Biochemistry.1984, 23:1532-1538
[112]Connor J, Norley N, Huang L. Biodistribution of pH-sensitive immunoliposomes. Biochim Biophys Acta.1986,884:474-481
[113]Kono K, Zenitani KI, Takagishi T. Noverl pH-sensitive liposomes:liposomes bearing a poly(ethylene glycol) derivative with catboxyl group. Biochim Biophys Acta.1994,1193: 1-9
[114]Sudimack JJ, Guo WJ, Tjarks W, Lee RJ. A novel pH-sensitive liposome formulation containing oleyl alcohol. Biochimica et Biophysica Acta.2002,1564:31-37
[115]符民桂,唐朝枢.pH敏感脂质体的研究进展.药学进展.1999,23:19-23
[116]Hafez IM, Ansell S, Cullis PR. Tunable pH-sensitive liposomes composed of mixtures of cationic and anionic lipids. BiophysJ.2000,79:1438-1446
[117]Roux E, Passirani C, Scheffold S, Benoit J-P, Leroux J-C. Serum-stable and long-circulating, PEGylated, pH-sensitive lipomes. Journal of Controlled Release.2004,94: 447-451
[118]Kono K, Henmi A, Yamashita H, Hayashi H, Takagishi T. Improvement of temperature-sensitivity of poly(N-ispropylacrylamide)-modified liposomes. Journal of Controlled Release.1999,59:63-75
[119]Drummond DC, Zignani M, Leroux J-C. Current status of pH-sensitive liposomes in drug delivery. Progress in Lipid Research 2000,39:409-460
[120]戈升荣,陈御石.聚合物表面结合pH—敏感型脂质小囊的制备及其pH—敏感性.上海医科大学学报.1998,4:251-254
[121]王汝涛,陈涛,王昭,惠民权,傅经国.酸敏高分子诱导的脂质体膜融合性能研究.药学学报.2008,9:951-955
[122]Ringsdorf H, Schlarb J, Venzmer J. Melecular architecture and function of polymeric oriented system:models for the sutdy of organization, surface recognition, and dynamics of bilmembrances. Angew Chem, Int Ed Engl.1988,27:113-158
[123]Thomas JL, Tirrell DA. Polyelectrolyte-sensitized phospholipid vesicles. Acc Chem Res.1992,25:336-342
[124]Slepushkin VA, Simoes S, Dazin P, Newman MS, Guo LS, Pedroso de Lima MC, Duzgunes N. Sterically stabilized pH-sensitive liposomes. Intracellular delivery of aqueous contents and prolonged circulation in vivo. J Biol Chem.1997,272:2382-2388
[125]Holland JW, Hui C, Cullis PK, Madden TD. Polyethylene glycol)-lipid conjugates regulate the calcium-induced fusion of liposomes composed of phosphatidylethanolamine and phosphatidylserine. Biochemistry.1996,35:2618-2624
[126]Kirpotin D, Hong K, Mullah N, Papahadjopoulos D. Liposomes with detachable polymer coating:Destabilization and fusion of dioleoylphosphatidylethanolamine vesicles triggered by cleavage of surface-grafted poly(ethylene glycol). FEBS Letter.1996,388: 115-118
[127]Maeda M, Kumano A, Tirrell DA. H+-induced release of contents of phosphatidylcholine vesicles bearing surface-bound polyelectrolyte chains. J Am Chem Soc. 1988,110:7455-7459
[128]Leroux JC, Roux E, Le GarrecDL, Hong K, Drummond DC. N-Isopropylacrylamide copolymers for the preparation of pH-sensitive liposomes and polymeric micelles. J Control Release.2001,72:71-84
[129]Ringsdorf H, Venzmer J, Winnik FM. Interaction of hydrophocially-modified poly-N-isopropylacrylamides with model membranes-or playing a molecular accordion. Angew Chem, Int Ed Engl.1991,30:315-318
[130]Polozova A, Winnik FM. Contribution of Hydrogen Bonding to the Association of Liposomes and an Anionic Hydrophobically Modified Poly(N-isopropylacrylamide). Langmuir.1999,15:4222-4229
[131]Kono K, Yoshino K, Takagishi T. Effect of poly(ethylene glycol) grafts on temperature-sensitivity of tbermosensitive polymer-modified liposomes.lournal of Controlled Release.2002,80:321-332
[132]Seki K, Tirrell DA. pH-Dependent complexation of poly(acrylic acid) derivatives with phospholipid vesicle membranes. Macromolecules.1984,17:1692-1698
[133]Chung JC, Gross DJ, Thomas JL, Tirrell DA, Opasahl-Ong LR. pH-sensitive, cation-selective channels formed by a simple synthetic polyelectrolyte in artificial bilayer membranes. Macromolecules.1996,29:4636-4641
[134]Yuba E, Kojima C, Harada A, Tana, Watarai S, Kono K. pH-Sensitive fusogenic polymer-modified liposomes as a carrier of antigenic proteins for activation of cellular immunity Biomaterials.2010,31:943-951
[135]Yuba E, Harada A, Sakanishi Y, Kono K. Carboxylated hyperbranched poly(glycidol)s for preparation of pH-sensitive liposomes Journal of Controlled Release.2011,149:72-80
[136]Echienbaum GM, Kiser PF, Dobrynin AV, Simon SA, Needham D. Investigation of the Swelling Response and Loading of Ionic Microgels with Drugs and proteins:The Dependence on Cross-Link Density. Macromolecules.1999,32(15):4867-4878
[137]Gan D, Lyon LA. Synthesis and Protein Adsorption Resistance of PEG-Modified Poly(N-isopropylacrylamide) Core/Shell Microgels. Macromolecules.2002,35(26): 9634-9639
[138]Debord JD, Lyon LA. Thermoresponsive Photonic Crystals. JPhysChem B.2000, 104(27):6327-6331
[139]Subrahmanyama CVS, Suresh S. Solubility behaviour of haloperidol in individual solvents determination of partial solubility parameters European Journal of Pharmaceutics and Biopharmaceutics.1999,47:289-294
[140]Lia QZ, Luo LF. The kinetic theory of thermal hysteresis of a macromolecule solution Chemical Physics Letters.1993,216:453-457
[141]Dimitrov I, Trzebicka B, Muller Axel HE, Dworak A, Tsetanov CB. Thermosensitive water-soluble copolymers with doubly responsive reversibly interacting entities. Prog Polym Sci.2007,32:1275-1343
[142]Lin JJ, Hsu YC. Temperature and pH-responsive properties of poly(styrene-co-maleic anhydride)-grafting poly(oxypropylene)-amines. Journal of Colloid and Interface Science. 2009,336:82-89
[143]Wang C, Flynn NT, Langer R. Controlled Structure and Properties of Thermoresponsive Nanoparticle-Hydrogel Composites. Adv Mater.2004,16:1074-1079
[144]Chang JH, Shim CH, Kim BJ, Shin Y, Exarhos GJ, Kim KJ, Bicontinuous. Thermoresponsive, L3-Phase Silica Nanocomposites and Their Smart Drug-Delivery Applications. Adv Mater.2005,17:634-637
[145]Hong SW, Kim KH, Huh J, Ahn CH, Jo WH. Design and Synthesis of a New pH Sensitive Polymeric Sensor Using Fluorescence Resonance Energy Transfer. Chem Mater. 2005,17:6213-6215
[146]Bromberg L, Temchenko M, Moeser GD, Hatton TA. Thermodynamics of Temperature-Sensitive Polyether-Modified Poly(acrylic acid) Microgels. Langmuir.2004,20: 5683-5692
[147]Zhang L, Guo R, Yang M, Jiang X, Liu B. Thermo and pH Dual-Responsive Nanoparticles for Anti-Cancer Drug Delivery. Adv Mater.2007,19:2988-2992
[148]Du J, Armes SP. pH-Responsive Vesicles Based on a Hydrolytically Self-Cross-Linkable Copolymer. J Am Chem Soc.127:12800-12801
[149]Khoukh S, Oda R, Labrot Th, Perrin P, Tribet C. Light-Responsive Hydrophobic Association of Azobenzene-Modified Poly(acrylic acid) with Neutral Surfactants. Langmuir. 2007,23:94-104
[150]Liu XM, Wang LS, Wang L, Huang J, He C. The effect of salt and pH on the phase-transition behaviors of temperature-sensitive copolymers based on N-isopropylacrylamide. Biomaterials.2004,25:5659-5666
[151]Debord JD, Lyon LA. Synthesis and Characterization of pH-Responsive Copolymer Microgels with Tunable Volume Phase Transition Temperatures. Langmuir.2003,19: 7662-7664
[152]Otake T, Inomata H, Konno M, Saito S. Numerical study of hydrodynamic radii of polymer chains in (?) solvent. Macromolecules.1990,23:283-289
[153]Tiktopulo El, Bychkova VE, Ricka J, Ptitsyn OB. Cooperativity of the Coil-Globule Transition in a Homopolymer:Microcalorimetric Study of Poly(N-isopropylacrylamide). Macromolecules.1994,27:2879-2882
[154]Han CK, Bae YH. Inverse thermally-reversible gelation of aqueous N-isopropylacrylamide copolymer solutions. Polymer.1998,39:2809-2814
[155]Bokias G, Staikos G, Iliopoulos I. Solution properties and phase behavior of copolymers of acrylic acid with N-isopropylacrylamide:the importance of the intrachain hydrogen bonding. Polymer.2000,41:7399-7405
[156]Kusonwieiyawong E, Wetering P, Hubbell JA, Merkle IIP, Walter E. Evaluation of pH-dependent membrane-disruptive properties of poly(acrylic acid) derived polymers. European Journal of Pharmaceutics and Biopharmaceutics.2003,56:237-246
[157]Amalvy JI, Wanless EJ, Michailidou YLY, Armes SP. Synthesis and Characterization of Novel pH-Responsive Microgels Based on Tertiary Amine Methacrylates. Langmuir.2004, 20:8992-8999
[158]Schimdt S, Motachmann H, Hwllweg T, Klitzing RV. Thermoresponsive surfaces by spin-coating of PNIPAM-co-PAA microgels:A combined AFM and ellipsometry study. Polymer.2008,49:749-756
[159]Zakir MR, Dincer S, Piskin E. Functional copolymers of N-isopropylacrylamide for bioengineering applications. Prog Polym Sci.2007,32:534-595
[160]Woodle MC, Papahadjopoulos D. Liposome preparation and size characterization. Methods in Enzymology.1989,171:193-217
[161]Inomata H, Goto S, Otake K, Saito S. Effect of additives on phase transition of N-isopropylacrylamide gels. Langmuir.1992,8:687-690
[162]Zignani M, Drummond DC, Meyer O, Hong K, Leroux J-C. In vitro characterization of a novel polymeric-based pH-sensitive liposome system. Biochimica et Biophysica Acta. 2000,1463:383-394
[163]Ni CH, Zhu XX, Wang QL, Zeng XY. Studies on LCST of poly(N-isopropylacrylamide-co-acrylic acid-co-N-diacetone acrylamide). Chinese Chemical Letters.2007,18:79-80
[164]Wei H, Zhang XZ, Cheng C, Cheng SX, Zhuo RX. Self-assembled thermoresponsive micelles of poly(N-isopropylacrylamide-b-methyl methacrylate). Biomaterials.2006,27: 2028-2034
[165]Yessine MA, Lafleur M, Meier C, Petereit HU, Leroux JC. Characterization of the membrane-destabilizing properties of different pH-sensitive methacrylic acid copolymers. Biochimica et Biophysica Acta.2003,1613:28-38
[166]Zhang JP, Wang AQ. pH- and thermo-responsive dispersion of single-walled carbon nanotubes modified with poly(N-isopropylacrylamide-co-acrylic acid). Journal of Colloid and Interface Science.2009,334:212-216
[167]Fei JQ, GU LX. PVA/PAA thermo-crosslinking hydrogel fiber:preparation and pH-sensitive properties in electrolyte solution. Europen Polymer Journal.2002,38: 1653-1658
[168]Yang XY, Chen LT, Huang B, Bai F, Yang XL. Synthesis of pH-sensitive hollow polymer microspheres and their application as drug carriers. Polymer.2009,50:3556-3563
[169]YuXi Z, FeiPeng W, MiaoZhen L, ErJian W. pH switching on-off semi-IPN hydrogel based on cross-linked poly(acrylamide-co-acrylic acid) and linear polyallyamine. Polymer. 2005,46:7695-7700
[170]Jamie O, Mona P, Anthony L, Dan N. Controlling the collapse/swelling transition in charged hydrogels. Biomaterials.2004,25:4345-4353
[171]Dayananda K, He C, Dong KP, Tae GP, Lee DS. pH- and temperature-sensitive multiblock copolymer hydrogels composed of poly(ethylene glycol) and poly(amino urethane). Polymer.2008,49:4968-4973
[172]Dayananda K, He C, Lee DS. In situ gelling aqueous solutions of pH- and temperature-sensitive poly(ester amino urethane)s. Polymer.2008,49:4620-4625
[173]Jian F, Honglai L, Ying H. Micro-phase separation of diblock copolymer in a nanosphere:Dissipative particle dynamics approach. Fluid Phase Equilibria.2007,261:50-57
[174]Xu H, Honglai L, Ying H. Dynamic density functional theory based on equation of state. Chemical Engineering Science.2007,62:3494-3501
[175]纪朝红,葛红江.调剖堵水材料研究现状与发展趋势.石油钻采工艺.2002,24(1):54-57
[176]史向阳,吴世康,孙曹民.疏水化修饰的聚N-异丙基丙烯酰胺高分子的水溶液性质研究.高分子学报.1999,2:16-25
[177]Taillefer J, Jones MC, Brasseur N, Van LJE, Leroux JC. Preparation and characterization of ph-responsive polymeric micelles for the delivery of photosensitizing anticancer drugs. Journal of Pharmaceutical Sciences.2000,89:52-62
[178]Roux E, Francis M, winnik FM, Leroux JC. Polymer based pH-sensitive carriers as a means to improve the cytoplasimic delivery of drug. International Journal of Pharmaceutics. 2002,242:25-36
[179]Gehrke S.H., Palasis M, Akhtar M.K. Effect of synthesis conditions on properties of poly(N-isopropylacrylamide) gels. Polymer International.1992,29:29-36
[180]Antonios K, Tian T, Vasiliki H, Kyriakos V, Lan WH. Micellar and surface properties of a poly(methyl methacrylate)-block-poly(N-isopropylacrylamide) copolymer in aqueous solution. Journal of Colloid and Interface Science.2008,320:70-73
[181]Shi XY, Wang SK. Water Solution Properties of Hydrophobically Modified Poly(N-isopropylacrylamides). Acta Polymerica Sinica.1999,2:16-23
[182]Cheon JB, Jeong Y, Cho CS. Effects of temperature on diblock copolymer micelle composed of poly(γ-benzyl -glutamate) and poly(N-isopropylacrylamide). Polymer.1999, 40:2041-2050
[183]Zhang W, Dong GJ, Yang H, Sun JH, Zhou JZ, Wang JB. Synthesis, surface and aggregation properties of a series of amphiphilic dendritic copolymers. Colloids and Surfaces A:Physicochem Eng Aspects.2009,348:45-48
[184]Fraaije JGEM, Vlimmeren BAC, Maurits MN, Postma M, Evers OA, Hoffman C, Altevogt P. The dynamics mean-field density functional method and its appliation to mesoscopic dynamics of quenched block copolymer melts. Journal of Chemical Physics.1997, 104:4260-4269
[185]Groot RD, Warren P. Dissipative Particle Dynamics:Bridging the gap between atomistic ans mesoscopic simulation. J Chem Phys.1997,107:4423-4435
[186]GAO C, Moehwald H, Shen J. Thermosensitive poly(allylamine)-g-poly(N-isopropylacrylamide):synthesis, phase separation and particle formation. Polymer.2005,46:4088-4097
[187]Wang LQ, Tu KH, Li YP, Zhang J. Phase Transtion and Micellization of Temperature Responsive Dextran-graft-poly(N-isopropylacrylamide) Polymers. Chinese Chemical Letters. 2003,14:407-410
[188]O'Lenick TG, Jiang XG, Zhao B. Thermosensitive Aqueous Gels with Tunable Sol-Gel Transition Temperatures from Thermo- and pH-Responsive Hydrophilic ABA Triblock Copolymer. Langmuir.2010,26:8787-8796
[189]Gan LH, Cai W, Tam KC. Sudies of phase transition of aqueous solution of poly(N,N-diethylacrylamide-co-acrylic acid) by differerntial scanning calorimetry and specrophotometry. European Polymer Journal 2001,37:1773-1778
[190]Herman F, You HB, Jan F, Sung WK. Effect of comonomer Hydrophilicity and ionization on the lower critical solution temperature of N-isopropylacrylamide copolymers. Macromolecules.1993,26:2496-2500
[191]Roux E, Lafleur M, Lataste E, Moreau P, Leroux JC. On the characterization of pH-sensitive liposome/polymer complexes. Biomacromolecules.2003,4:240-248
[192]Feil H, Bae YH, Feijen J, Kim SW. Effect of comonomer hydrophilicity and ionization on the lower critical solution temperature of N-isopropylacrylamide copolymers. Macromolecules.1993,26:2496-2500
[193]Vemuri S, Rhodes CT. Preparation and characterization of liposomes as therapeutic delivery systems:a review Pharmaceutica Acta Helvetiae.1995,70:95-111
[194]Schuch H, Klingler J, Rossmanith P, Frechen T, Gerst M, Feldthusen J, Muller AHE. Characterization of micelles of polyisobutylene-block-poly(methacrylic acid) in Aqueous Medium. Macromolecules.2000,33:1734-1740
[195]Zhou WT, An XQ, Gong J, Shen WG, Chen ZY, Wang XY Synthesis, characteristics and phase behaviour of a thermosensitive and pH-sensitive polyelectrolyte. Journal of applied polymer science.2011,121:2089-2037
[196]Gao C, Mohwald H, Shen J. Thermosensitive poly(allylamine)-g-poly(N-isopropylacrylamide):synthesis, phase separation and paricel formation. Polymer.2005,46:4088-4097
[197]Liu S, Weaver J, Save M, Armes S. Synthesis of pH-responsive shell cross-linked micelles and their use as nanoreactors for the preparation of gold nonoparticles. Langmuir. 2002,18:8350-8357
[198]Cho EC, Lim HJ, Kim HJ, Son ED, Choi HJ, Park JH, Kim JW, Kim J. Role of pH-sensitive polymer-liposome complex in enhancing cellular uptake of biologically active drugs. Materials Science and Engineering C.2009,29:774-778
[199]Asgharian N, Schelly ZA. Electric field-induced transient birefringence and light scattering of synthetic liposomes Biochimica et Biophysica Acta.1999,1418:295-306
[200]Kono K, Hayashi H, Takagishi T. Temperature-sensitive liposomes:liposomes bearing poly (N-isopropylacrylamide) Journal of Controlled Release.1994,30:69-75
[201]Kim JC, Kim JD. Release property of temperature-sensitive liposome containing poly(N-isopropylacrylamide). Colloids and Surfaces B:Biointerfaces.2002,24:45-52
[202]Paoli EE, Kruse D, Seo JW, Zhang H, Kheirolomoom A, Watson KD, Chiu P, Stahlberg H, Ferrara KW. An optical and microPET assessment of thermally-sensitive liposome biodistribution in the Met-1 tumor model:Importance of formulation. Journal of Controlled Release.2010,143:13-22
[203]Kono K, Yoshino K, Takagishi T. Effect of poly(ethylene glycol) grafts on temperature-sensitivity of thermosensitive polymer-modified liposomes. Journal of Controlled Release.2002,80:321-332
[204]Viroonchatapan E, Sato H, Ueno M, Adachi I, Tazawa K, Horikoshi I. Magnetic targeting of thermosensittve magnetoliposomes to mouse livers in an in situ on-line perfusion system. Life Sciences.1996,58:2251-2261
[205]Dandamudi S, Campbell RB. Development and characterization of magnetic cationic liposomes for targeting tumor microvasculature. Biochimica et Biophysica Acta.2007,1768: 427-438
[206]Nakao R, Matuo Y, Mishima F, Taguchi T, Maenosono S, Nishijima S. Development of magnetic separation system of magnetoliposomes. Physica C:Superconductivity.2009,469: 1840-1844
[207]Wardak A, Brodowski R, Krupa Z, Gruszecki WI. Effect of light-harvesting complex II on ion transport across model lipid membranes Journal of Photochemistry and Photobiology B:Biology.2000,56:12-18
[208]Christina RM, Paula JC, David FO. Visible light-induced destabilization of endocytosed liposomes. FEBS Letters.2000,467:52-56
[209]Turk MJ, Reddy JA, Chmielewski JA, Low PS. Characterization of a novel pH-sensitive peptide that enhances drug release from folate-targeted liposomes at endosomal pHs Biochimica et Biophysica Acta.2002,1559:56-68
[210]Maitani Y, Igarashi S, Sato M, Hattori Y. Cationic liposome (DC-Chol/DOPE=1:2) and a modified ethanol injection method to prepare liposomes, increased gene expression. International Journal of Pharmaceutics.2007,342:33-39
[211]Ding WX, Qi XR, Li P, Maitani Y, Nagai T. Cholesteryl hemisuccinate as a membrane stabilizer in dipalmitoylphosphatidylcholine liposomes containing saikosaponin-d. International Journal of Pharmaceutics.2005,300:38-47
[212]Lai MZ, Vail JW, Szoka FC. Acid- and Calcium-Induced Structural Changes in Phosphatidylethanolamine Membranes Stabilized by Cholesteryl Hemisuccinatet. Biochemistry.1985,24:1654-1661
[213]Zhao XB, Lee RJ. Tumor-selective targeted delivery of genes and antisense oligodeoxyribonucleotides via the folate receptor Advanced Drug Delivery Reviews.2004,56: 1193-1204
[214]Fonseca C, Moreira JN, Ciudad CJ, Pedroso MC, Simoes S. Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells European Journal of Pharmaceutics and Biopharmaceutics.2005,59:359-366
[215]Suzuki S, Watanabe S, Masuko T, Hashimoto Y. Preparation of long-circulating immunoliposomes containing adriamycin by a novel method to coat immunoliposomes with poly(ethylene glycol) Biochimicaet Biophysica Acta.1995,1245:9-16
[216]Zeng XJ, Zeng XH. Relationship between the clinical effects of berberine on severe congestive heart failure and its concentration in plasma studied by HPLC. Biomedical Chromatograhy.1999,13 (7):442-444
[217]R.G Kinga, R.M. Marchbanks. The effect of pH on the size of liposomes formed by cholate dialysis. Biochimica et Biophysica Acta.1982,691:183-187
[218]Kono K, Henmi A, Yamashita H, Hayashi H, Takagishi T. Improvement of temperature-sensitivity of poly(N-isopropylacrylamide)-modified liposomes. Journal of Controlled Release.1999,59:63-75
[219]Mikes V, Kovar J. Interaction of liposomes with homologous series of fluorescent berberine derivatives:New cationic probes for measuring membrane potential Biochimica et Biophysica Acta (BBA)-Biomembranes.1981,640:341-351
[220]Fueldner HH. Characterization of a third phase transition in multilamellar dipalmitoyllecithin liposomes. Biochemistry.1981,20:5707-5710
[221]Lewis BA, Das Gupta SK, Griffin RG. Solid-state NMR studies of the molecular dynamics and phase behavior of mixed-chain phosphatidylcholines. Biochemistry.1984,23: 1988-1993
[222]Takeuchi H, Yamamoto H, Toyoda T. Physical stability of size controlled small unilameller liposomes coated with a modified polyvinyl alcohol. International Journal of Pharmaceutics.1998,164:103-111
[223]MC W. Controlling liposome blood clearance by surface-grafted polymers. Advanced Drug Delivery Reciews.1998,32:139-152
[224]Yang X, Lee HY, You SG, Kim JC. pH- and temperature-dependent release from cationic vesicles coexisting with copolymer of N-isopropylacrylamide and methacrylic acid. Colloids and Surfaces A:Physicochemical and Engineering Aspects.2009,348:109-115
[225]Ringsdorf H, Sackmann E,Simon J, Winnik FM. Interactions of liposomes and hydrophobically-modified poly-(N-isopropylacrylamides):an attempt to model the cytoskeleton. Biochimica et Biophysica Acta (BBA)-Biomembranes.1993,1153:335-344
[226]An XQ, Zhang F, Zhu YY, Shen WG. Photoinduced drug release from thermosensitive AuNPs-liposome using a AuNPs-switch. Chem Commun.2010,46:7202-7204
[227]Kono K, Hayashi H, Takagishi T. Temperature-sensitive liposomes:liposomes bearing poly (N-isopropylacrylamide). Journal of Controlled Release.1994,30:69-75
[228]Makino K, Yamada T, Kimura M, Oka T, Ohshima H, Kondo T. Temperature-and ionic strength-induced conformational changes in the lipid head group region of liposomes as suggested by zeta potential data Biophys Chem 1991,41:175-183
[229]Sabin J, Ruso JM, Gonzalez-Perez A, Prieto G, Sarmiento F. Characterization of phospholipid+semifluorinated alkane vesicle system. Colloids and Surfaces B:Biointerfaces. 2006,47:64-70
[2]陈智强.SMA树脂工艺过程的中试研究.合成树脂及塑料.2000,5:65-66
[3]姜忠民,黎华明.苯乙烯—马来酸酐无规共聚物合成研究.弹性体.1998,1(6-9):
[4]焦健,丁春黎.苯乙烯—马来酸酐无规共聚物的合成.吉林工学院学报：自然科学版.2001,3(22)：51-53
[5]单国荣,陈伟国.苯乙烯与N—苯基马来酰亚胺本体共聚合动力学.化学反应工程与工艺.1996,3(12)：225-231
[6]潘祖仁.高分子化学.化学工业出版社,1997年6月.
[7]惠远峰,张立东,徐崇利,包海峰.氟代丙烯酸酯/MAA共聚物合成工艺研究.化工新型材料.2010,5:103-105
[8]钱静.烯丙基聚乙醇一丙烯酸共聚物合成工艺及分散性能研究.中国建材科技.2011,2：64-67
[9]王国祥,肖永峰.丙烯酸与丙烯酰胺的反相悬浮共聚合的研究.石化技术.2010,3:1-4
[10]金关泰.高分子化学的理论和应用进展.中国石化出版社,1995年3月.
[11]赵明,王荣民,张慧芳,李宏洲.反相乳液聚合制备丙烯酰胺-二甲基二烯丙基氯化铵阳离子共聚物.甘肃高师学报.2010,2(15)：20-23
[12]赵群,倪沛红,常华.两亲性高分子乳化剂的苯乙烯乳液聚合研究.精细石油化工进展.2009,5：41-43
[13]虞志光.高聚物分子量及其分布的测定.上海科学技术出版社,1984年7月.
[14]郑昌仁.高聚物分子量及其分布.化学工业出版社,1986年7月.
[15]殷敬华,莫志深.现代高分子物理学 (上册).科学出版社,2001年.
[16]何平笙,杨海洋,朱平平,瞿保均.高分子物理实验.中国科技大学出版社,2002年.
[17]杨玉良,胡汉杰.高分子物理.化工出版社,2001年.
[18]Webber ST, Munk P, Tuzar Z. S. Netherlands:Kluwer Academic Publishers,1996.
[19]Zhang LF, Eisenberg A. Formation of crew-cut aggregates of various morphologies from amphiphilic block copolymers in solution. Polymers for advanced technologies.1998,9: 677-699
[20]Zhang LF, EIsenberg A. Multiple Morphologies of "Crew-Cut" Aggregates of Polystyrene-b-poly(acrylic acid) Block Copolymers Science.1995,23:1728-1731
[21]Zhang LF, Eisenberg A. Multiple Morphologies and Characteristics of "Crew-Cut" Micelle-like Aggregates of Polystyrene-b-poly(acrylic acid) Diblock Copolymers in Aqueous Solutions. J Am Chem Soc.1996,118:3168-3181
[22]Aoi K, Tsutsamiuchi K, Okada M. Glycopeptide Synthesis by an.alpha.-Amino Acid N-Carboxyanhydride (NCA) Method:Ring-Opening Polymerization of a Sugar-Substituted NCA. Macromolecules.1994,27:875-877
[23]Kobayashi K, Tsuchida A, Usui T, Akaike T. A New Type of Artificial Glycoconjugate Polymer:A Convenient Synthesis and Its Interaction with Lectins. Macromolecules.1997,30: 2016-2020
[24]梁玉增,李子臣,李福绵.两亲性含糖嵌段共聚物在水中分子聚集形态的转变.高等学校化学学报.1999,11：1820-1822
[25]徐祖顺,封麟先,易昌凤,陈永春,程时远.两亲聚合物溶液性质及其乳液聚合的研究进展.高分子材料科学与工程.1998,14:1-4
[26]崔正刚.溶液表面化学.无锡轻工业大学,2001年2月.
[27]崔正刚,殷福珊.微乳化技术及应用.中国轻工业出版社,1999年2月.
[28]胡志标,王永强,曾广鹏,张超,夏必来,洪昕林,张高勇.催化链转移聚合制备接枝型两亲共聚物及其溶液性质研究.化学学报.2007,23：2656-2662
[29]Jhaveri SB, Koylu D, Maschke D, Carter KR. Synthesis of Polymeric Core-Shell Particles Using Surface-Initiated Living Free-Radical Polymerization. Journal of Polymer Science:Part A:Polymer Chemistry.2007,45:1575-1584
[30]Motornov M, Roiter Y, Tokarev I, Minko S. Stimuli-responsive nanoparticles, nanogels and capsules for integrated multifunctional intelligent systems. Progress in Polymer Science.2010,35:174-211
[31]Carlsen A, Lecommandoux S. Self-assembly of polypeptide-based block copolymer amphiphiles. Current Opinion in Colloid & Interface Science.2009,14:329-339
[32]Riess G, Hurtrez G, Babadur P. Encyclopedia of polymer science. New York:Wiley, 1985.
[33]徐祖顺,易昌凤,程时远.聚甲基丙烯酸甲酯接枝聚氧乙烯共聚物溶液性质的研究.高分子学报.2000,6:701-706
[34]Wu Chi. A slmplemodelforthe structure of sphedcalmicroemulsion. Macromolecules. 1994,27:298-299
[35]Sikora A, Tuzar Z. Association of two-block copolymer polystyrene—block-(2-vinylpyridine)in toluene. Makromol Chem.1983,184:2049-2059
[36]Astafieva I, Zhong XF, Eisenberg A. Critical micellization phenomena in block polyelectrolyte solution. Macromolecules.1993,26:7339-7352
[37]Quintana JR, Villacampa M, Katime IA. Micellization of apolystyrene-b-poly(ethylene/propylene)block copo lymer in n-dodecane/1,4-dioxane mloxanc mixtures(2):Structure and dimensions of micelles. Macromolecules.1993:606-611
[38]Kwon GS, Kataoka K. Block copolymer micelles as long-criculating drug vehicles. Advanced Drug Delivery Reviews.1995,16:295-309
[39]Jones M-C, Leroux J-C. Polymeric micelles-a new generation of colloidal drug carriers European Journal of Pharmaceutics and Biopharmaceutics.1999,48:101-111
[40]Yokoyama M, Sugiyama T, Okano T, Sakurai Y, Naito M, Kataoka K. Analysis of micelle formation of an adriamycinconjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer by gel permeation chromatography. Pharm Res.1993,10:895-899
[41]Nishiyama N, Kataoka K. Preparation and characterization of size-controlled polymeric micelle containing cis-dichloro-diammineplatinum (II) in the core. Journal of Controlled Release.2001,74:83-94
[42]Zhang JX, Qiu LY, Jin Y, Zhu KJ. Controlled nanoparticles formation by self-assembly of novel amphiphilic polyphosphazenes with poly(N-isopropylacrylamide) and ethyl glycinate as side groups. Reactive & Functional Polymers.2006,66:1630-1640
[43]Ma X, Cui Y, Zhao X, Zheng S, Tang XZ. Different deswelling behavior of temperature-sensitive microgels of poly(N-isopropylacrylamide) crosslinked by polyethyleneglycol dimethacrylates. Journal of Colloid and Interface Science.2004,276: 53-59
[44]Li Z, Xiong D, Xu B, Wu C, An YL, Ma RJ, Shi LQ. Fabrication of an asymmetric hollow particle with a thermo-sensitive PNIPAM inside corona. Polymer.2009,50:825-831
[45]Nie T, Zhao Y, Xie Z, Wu C. Micellar formation of poly(caprolactone-block-ethylene oxide-block-caprolactone) and its enzymatic biodegradation in aqueous dispersion. Macromolecules.2003,36:8825-8829
[46]Allen C, Maysinger D, A, E. Nano-engineering block copolymer aggregates for drug delivery. Colloids and Surfaces B:Biointerfaces.1999,16:3-27
[47]Zhang L, Hu Jiang X. Camptothecin derivative-loaded poly(caprolactone-co-lactide)-b-PEG-b-poly(caprolactone-co-lactide)nanoparticles and their biodistribution in mice. Journal of Controlled Release.2004,96:135-148
[48]Mrkic J, Saunders BR. Microgel Particles as a Matrix for Polymerization:A Study of Poly(N-isopropylacrylamide)-Poly(N-methylpyrrole) Dispersions. Journal of Colloid and Interface Science.2000,222:75-82
[49]Tsitsilianis C, Sfika V. Heteroarm star-like micelles formed from polystyrene-block-poly(2-vinyl pyridine)-block-poly(-methyl methacrylate) ABC copolymers in toluene. Macromlo Rapid Commoun.2001,22:647-651
[50]Wang X, Winnik M, Manners I. Synthesis and solution selfassembly of coil-crystalline-coil polyferrocenylphosphineb-polyferrocenylsilane-b-polysiloxane triblock copolymers. Macromolecules.2002,35:9748-9755
[51]Alexandridis P, Holzwarth JF, Alan Hatton T. Micellization of poly(ethyleneoxide) poly(propylene oxide)-poly(ethylene oxide)triblock copolymers in aqueous solutions thermodynamics of copolymer association. Macromolecules.1994,27:2414-2425
[52]Chung JE, Yokoyama M, Aoyagi T. Effect of molecular architecture of hydrophobically modified poly(N-isopropylacrylamide) on the formation of thermoresponsive core-shell micellar's drug carriers. Controlled Release.1998,53:119-130
[53]Dowding PJ, Vincent B, Williams E. Preparation and Swelling Properties of Poly(NIPAM) "Minigel" Particles Prepared by Inverse Suspension Polymerization. Journal of Colloid and Interface Science.2000,221:268-272
[54]徐祖顺,陈中华,陈焕钦,封麟先.用粘度法研究PMMA-g-PEO在甲苯中微胶束的形成.华南理工大学学报.2000,9:114-119
[55]EB, J, Hvidt S, Brown W. Effectsofsalts on the micellization and gelation of a triblock copolymer studied by rhelogy and light scattering. Macromolecules.1997,30: 2355-2364
[56]Bahadur P, Pandya K, Almgen M. Effect of inorganic salts on the micellar behavior of ethylene oxide—propylene oxide block copolymer in aqueous solution. Colloids Polymer science.1993,271:657-667
[57]赵锦花,孙多先.两亲接枝共聚物PECA-g-PEG胶束的CMC及表面带电性.应用化学.2004,8：844-846
[58]赵国玺.表面活性剂物理化学.北京大学出版社,1991年.
[59]K.霍姆博格,琼森B,科隆博格 B,林德曼B.水溶液中的表面活性剂和聚合物(原著第二版).化学工业出版社,200年3月.
[60]Rosen MJ. Surfactans and Interfacial Phenomena. Wiley Interscience, New York, 1989.
[61]La SB, Okano T, Kataoka K. Preparation and characterization of the micelle-forming polymeric drug indomethacinincorporated poly(ethylene oxide)-poly(betabenzyl 1-aspartate) block copolymer micelles. J Pharm Sci.1996,85:85-90
[62]Kabanov AV, Batrakova EV, Alakhov VY. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release.2002,82:189-212
[63]施斌,方超,裴元英.两亲性嵌段共聚物胶束的研究进展.中国医药工业杂志.2005,36：239-243
[64]Capek I. Fate of excited probes in micellar systems. Advanced Colloied Interface Science.2002,97:91-149
[65]徐金军,倪忠斌,陈明清PMMA-g-PEG的制备及其相转变性能研究.化工新型材料 2008,8:51-53
[66]胡吉,周光宇,陈彦模,朱美芳.相变调温PFT-PEG嵌段共聚物的性能和结构的 研究.东华大学学报.2006,3：105-109
[67]曾钫,刘新星.NIPA/DMAA共聚物及其水溶液相转变温度的研究.高分子材料科学与工程.1997,5:100-103
[68]Caillol S, Lecommandoux S, Mingotaud A.-F, Schappacher M, Soum A, Bryson N, Meyrueix R. Synthesis and self-assembly properties of peptide-polylactide block copolymers. Macromolecules.2003,36:1118-1124
[69]Qiu XY, Wang CQ, Shen J, Jiang MW. Controlled synthesis of amphiphilic rod-coil biodegradable maltoheptaose-graft-poly(-caprolactone) copolymers. Carbobydrate Polymers. 2011,83:1723-1729
[70]Guohua Chen, Allan S. Hoffman. Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH. Nature.1995,373:49-52
[71]Kiler J, Scranton AB, Peppas NA. Self-associating networks of poly(methacrylic acid-g-ethylene glycol). Macromolecules.1990,23:4944-4949
[72]李芳,刘守信,刘侠,张朝阳,余娟,房喻.温度/pH双敏感性接枝共聚物P(MAA-g-NIPAM)相行为研究.陕西师范大学学报.2007,3：52-56
[73]余娟丽,李守信,房喻,高改玲,王明珍.温度/pH敏感性P(MAA-g-DEAM)共聚物水溶液的相行为.物理化学学报.2006,22:579-583
[74]徐华,宋涛.磁性药物靶向治疗的发展.国外医学生物医学工程分册.2004,27:61-64
[75]贾利军,王德,余国芬,张怀武.磁性药物载体的合成.材料导报.2004,18:66-71
[76]Jodan A, Wuat P, Scholz R. Effects of magnetic fluid hyperthermia (MFH) on C3H mamary carcinoma in vivo. Int J Hyperthermia.1997,13:587
[77]张阳德,龚连生.磁性阿霉素白蛋白纳米粒的研制.中国现代医学杂志.2001,3:1-3
[78]王尊元,马臻.高分子及高分子药物在现代医药上的应用.浙江省医学科学院学报.1998,6：45-47
[79]纳榕,张强华.高分子载体在药物控释体系中的应用.淮阴工学院学报.2004,13:81-83
[80]李玲.纳米药物载体的研究.材料导报.2002,16:58-59
[81]罗毅,卓仁禧,范昌烈.短肽5-氟尿嘧啶前体药物的合成及其抗肿瘤活性研究.高等学校化学学报.1994,15：545-547
[82]Chelvi PT. Heat-mediated selective delivery of Liposome-associated melphalam in murine melanoma. Melanona Res.1995,5:321-326
[83]李立新,樊品,王学谦.脂质体包裹人血红蛋白微囊的制备及其对大鼠血液的影响.天津医药.2004,32：p101-103
[84]纪俊敏,谢文磊.脂质体作为药物载体的研究进展.郑州工程学院学报.2002,23: 68-72
[85]冯杨,马玉坤,周华晨,瞿光喜.新型脂质体的研究与应用.山东医药.2004,44:59-60
[86]肖超,吴新荣.紫杉醇磁性脂质体的制备与抗肿瘤作用研究.医药导报.2010,11：1401-1404
[87]周伟华,郭讯枝,张阳德,何剪太,曾昭武,刘星言,谭斐,赵劲风,潘一峰.纳米司莫司汀磁性脂质体的制备及表征.科技通报.2008,3:406-410
[88]黄义昆.脂质体作为药物载体研究进展.中国药师.2005,8:549-550
[89]郜海涛,顾黎,张鹏英,孔蕴,陈靠山,王鹏.牛蒡寡糖脂质体的制备和性质鉴定.科技通报.2010,6:863-868
[90]张方宇,何松.乳糖脂修饰苦参碱脂质体的肝靶向性和体外抑瘤作用研究.重庆医科大学学报.2009,6:747-751
[91]景恒翠,王国生,于阳.肺靶向穿心莲内酯脂质体的制备及体外释放特征.亚太传统医药.2010,8:41-42
[92]傅刘鹏,徐俊,黄思超,邱胜红,蔡绍晖.叶酸脂质体对乳腺癌4T1细胞的体内靶向性研究.山东医药.2010,7:23-25
[93]张丙杰,迟令懿,李永刚,祝侠丽,李牧,张娜,滕良珠,朱树干.热敏脂质体洛莫司汀热靶向化疗的实验研究.中华物理医学与康复杂志.2007,5:316-317
[94]董兰凤,赵兴茹,冯凤莲,范美菊,杨丽.阿霉素长循环热敏脂质体的研制及其靶向治疗肿瘤作用的研究.中国肿瘤生物治疗杂志.2005,1:52-56
[95]Wen SY, wang XH, Lin L, Guan W, Wang SQ. Preparation and property analysis of a hepatocyte targeting pH-sensitive liposome. World Journal of Gastroenterology.2004,2: 244-249
[96]王弘,王升启.反义寡核苷酸pH敏前体脂质体的制备及性质分析.生物化学与生物物理进展.2000,2:178-181
[97]曹宁宁,羡非,刘鹏.脂质体的制备方法及研究进展.天津理工学院学报.2003,19：30-35
[98]温演庆,杨斌,钱志勇.光敏纳米脂质体制备及其特性研究.中国医学工程.2008,2：84-85
[99]袁有成,易学瑞,祖萍,张宜俊.新型佐剂及其与重组HBsAg结合物的理化性质的研究.中国生物制品学杂志.2003,3：168-171
[100]李津明,张彦卓,朱宇,任君刚,李鑫.依托泊苷隐形脂质体的制备及其质量评价.中国医药工业杂志.2008,39:834-837
[101]汪多仁.卵膦脂脂质体开发与应用进展.化工中间体.2003,10:23-26
[102]张晶,杨静,吴基良,张琳.异甘草素脂质体的制备及稳定性考察.25.2005:1046-1048
[103]段逸松,于波涛,张志荣.米托蒽醌长循环脂质体的制备及药代动力学的研究.药学学报.2002,37:465-468
[104]夏书芹,许时婴.吐温80增溶-紫外分光光度法测定辅酶Q10脂质体的载量及包封率.食品与发酵工业.2005,10:131-135
[105]Frederiken L, Anton K, Hoogevest PV. Preparation of liposomes encapsulating water soluble compounds using supercritical carbon dioxide. J Pharm Sci.1997,86:921
[106]严宾,安学勤,白晶,张英华.超临界CO2法制备头孢唑啉钠脂质体.物理化学学报.2006,22：226-229
[107]文震,刘波,李琼,郑宗坤,游新奎,蒲一涛.超临界C02快速膨胀制备鱼腥草挥发油脂质体.过程工程学报.2009,9:350-354
[108]Simoes S, Moreira NJ, Fonseca C, Duzgunes N, Maria C, Lima PD. On the formulation of pH-sensitive liposomes with long circulation times. Advanced Drug Delivery Reviews.2004,56:947-965
[109]戈升荣,裴元英.pH敏感型脂质体释药机制研究概况.中国医药工业杂志.1998,29：564-568
[110]Hafez MI, Cullis PR. Roles of lipid polymorphism in intracellular delivery. Advanced Drug Delivery Reviews.2001,47:139-148
[111]Ellens H, Bentz J, Szoka FC. pH-induced destabilization of phosphatidylethanolamine-containing liposomes:Role of bilayer contact. Biochemistry.1984, 23:1532-1538
[112]Connor J, Norley N, Huang L. Biodistribution of pH-sensitive immunoliposomes. Biochim Biophys Acta.1986,884:474-481
[113]Kono K, Zenitani KI, Takagishi T. Noverl pH-sensitive liposomes:liposomes bearing a poly(ethylene glycol) derivative with catboxyl group. Biochim Biophys Acta.1994,1193: 1-9
[114]Sudimack JJ, Guo WJ, Tjarks W, Lee RJ. A novel pH-sensitive liposome formulation containing oleyl alcohol. Biochimica et Biophysica Acta.2002,1564:31-37
[115]符民桂,唐朝枢.pH敏感脂质体的研究进展.药学进展.1999,23:19-23
[116]Hafez IM, Ansell S, Cullis PR. Tunable pH-sensitive liposomes composed of mixtures of cationic and anionic lipids. BiophysJ.2000,79:1438-1446
[117]Roux E, Passirani C, Scheffold S, Benoit J-P, Leroux J-C. Serum-stable and long-circulating, PEGylated, pH-sensitive lipomes. Journal of Controlled Release.2004,94: 447-451
[118]Kono K, Henmi A, Yamashita H, Hayashi H, Takagishi T. Improvement of temperature-sensitivity of poly(N-ispropylacrylamide)-modified liposomes. Journal of Controlled Release.1999,59:63-75
[119]Drummond DC, Zignani M, Leroux J-C. Current status of pH-sensitive liposomes in drug delivery. Progress in Lipid Research 2000,39:409-460
[120]戈升荣,陈御石.聚合物表面结合pH—敏感型脂质小囊的制备及其pH—敏感性.上海医科大学学报.1998,4:251-254
[121]王汝涛,陈涛,王昭,惠民权,傅经国.酸敏高分子诱导的脂质体膜融合性能研究.药学学报.2008,9:951-955
[122]Ringsdorf H, Schlarb J, Venzmer J. Melecular architecture and function of polymeric oriented system:models for the sutdy of organization, surface recognition, and dynamics of bilmembrances. Angew Chem, Int Ed Engl.1988,27:113-158
[123]Thomas JL, Tirrell DA. Polyelectrolyte-sensitized phospholipid vesicles. Acc Chem Res.1992,25:336-342
[124]Slepushkin VA, Simoes S, Dazin P, Newman MS, Guo LS, Pedroso de Lima MC, Duzgunes N. Sterically stabilized pH-sensitive liposomes. Intracellular delivery of aqueous contents and prolonged circulation in vivo. J Biol Chem.1997,272:2382-2388
[125]Holland JW, Hui C, Cullis PK, Madden TD. Polyethylene glycol)-lipid conjugates regulate the calcium-induced fusion of liposomes composed of phosphatidylethanolamine and phosphatidylserine. Biochemistry.1996,35:2618-2624
[126]Kirpotin D, Hong K, Mullah N, Papahadjopoulos D. Liposomes with detachable polymer coating:Destabilization and fusion of dioleoylphosphatidylethanolamine vesicles triggered by cleavage of surface-grafted poly(ethylene glycol). FEBS Letter.1996,388: 115-118
[127]Maeda M, Kumano A, Tirrell DA. H+-induced release of contents of phosphatidylcholine vesicles bearing surface-bound polyelectrolyte chains. J Am Chem Soc. 1988,110:7455-7459
[128]Leroux JC, Roux E, Le GarrecDL, Hong K, Drummond DC. N-Isopropylacrylamide copolymers for the preparation of pH-sensitive liposomes and polymeric micelles. J Control Release.2001,72:71-84
[129]Ringsdorf H, Venzmer J, Winnik FM. Interaction of hydrophocially-modified poly-N-isopropylacrylamides with model membranes-or playing a molecular accordion. Angew Chem, Int Ed Engl.1991,30:315-318
[130]Polozova A, Winnik FM. Contribution of Hydrogen Bonding to the Association of Liposomes and an Anionic Hydrophobically Modified Poly(N-isopropylacrylamide). Langmuir.1999,15:4222-4229
[131]Kono K, Yoshino K, Takagishi T. Effect of poly(ethylene glycol) grafts on temperature-sensitivity of tbermosensitive polymer-modified liposomes.lournal of Controlled Release.2002,80:321-332
[132]Seki K, Tirrell DA. pH-Dependent complexation of poly(acrylic acid) derivatives with phospholipid vesicle membranes. Macromolecules.1984,17:1692-1698
[133]Chung JC, Gross DJ, Thomas JL, Tirrell DA, Opasahl-Ong LR. pH-sensitive, cation-selective channels formed by a simple synthetic polyelectrolyte in artificial bilayer membranes. Macromolecules.1996,29:4636-4641
[134]Yuba E, Kojima C, Harada A, Tana, Watarai S, Kono K. pH-Sensitive fusogenic polymer-modified liposomes as a carrier of antigenic proteins for activation of cellular immunity Biomaterials.2010,31:943-951
[135]Yuba E, Harada A, Sakanishi Y, Kono K. Carboxylated hyperbranched poly(glycidol)s for preparation of pH-sensitive liposomes Journal of Controlled Release.2011,149:72-80
[136]Echienbaum GM, Kiser PF, Dobrynin AV, Simon SA, Needham D. Investigation of the Swelling Response and Loading of Ionic Microgels with Drugs and proteins:The Dependence on Cross-Link Density. Macromolecules.1999,32(15):4867-4878
[137]Gan D, Lyon LA. Synthesis and Protein Adsorption Resistance of PEG-Modified Poly(N-isopropylacrylamide) Core/Shell Microgels. Macromolecules.2002,35(26): 9634-9639
[138]Debord JD, Lyon LA. Thermoresponsive Photonic Crystals. JPhysChem B.2000, 104(27):6327-6331
[139]Subrahmanyama CVS, Suresh S. Solubility behaviour of haloperidol in individual solvents determination of partial solubility parameters European Journal of Pharmaceutics and Biopharmaceutics.1999,47:289-294
[140]Lia QZ, Luo LF. The kinetic theory of thermal hysteresis of a macromolecule solution Chemical Physics Letters.1993,216:453-457
[141]Dimitrov I, Trzebicka B, Muller Axel HE, Dworak A, Tsetanov CB. Thermosensitive water-soluble copolymers with doubly responsive reversibly interacting entities. Prog Polym Sci.2007,32:1275-1343
[142]Lin JJ, Hsu YC. Temperature and pH-responsive properties of poly(styrene-co-maleic anhydride)-grafting poly(oxypropylene)-amines. Journal of Colloid and Interface Science. 2009,336:82-89
[143]Wang C, Flynn NT, Langer R. Controlled Structure and Properties of Thermoresponsive Nanoparticle-Hydrogel Composites. Adv Mater.2004,16:1074-1079
[144]Chang JH, Shim CH, Kim BJ, Shin Y, Exarhos GJ, Kim KJ, Bicontinuous. Thermoresponsive, L3-Phase Silica Nanocomposites and Their Smart Drug-Delivery Applications. Adv Mater.2005,17:634-637
[145]Hong SW, Kim KH, Huh J, Ahn CH, Jo WH. Design and Synthesis of a New pH Sensitive Polymeric Sensor Using Fluorescence Resonance Energy Transfer. Chem Mater. 2005,17:6213-6215
[146]Bromberg L, Temchenko M, Moeser GD, Hatton TA. Thermodynamics of Temperature-Sensitive Polyether-Modified Poly(acrylic acid) Microgels. Langmuir.2004,20: 5683-5692
[147]Zhang L, Guo R, Yang M, Jiang X, Liu B. Thermo and pH Dual-Responsive Nanoparticles for Anti-Cancer Drug Delivery. Adv Mater.2007,19:2988-2992
[148]Du J, Armes SP. pH-Responsive Vesicles Based on a Hydrolytically Self-Cross-Linkable Copolymer. J Am Chem Soc.127:12800-12801
[149]Khoukh S, Oda R, Labrot Th, Perrin P, Tribet C. Light-Responsive Hydrophobic Association of Azobenzene-Modified Poly(acrylic acid) with Neutral Surfactants. Langmuir. 2007,23:94-104
[150]Liu XM, Wang LS, Wang L, Huang J, He C. The effect of salt and pH on the phase-transition behaviors of temperature-sensitive copolymers based on N-isopropylacrylamide. Biomaterials.2004,25:5659-5666
[151]Debord JD, Lyon LA. Synthesis and Characterization of pH-Responsive Copolymer Microgels with Tunable Volume Phase Transition Temperatures. Langmuir.2003,19: 7662-7664
[152]Otake T, Inomata H, Konno M, Saito S. Numerical study of hydrodynamic radii of polymer chains in (?) solvent. Macromolecules.1990,23:283-289
[153]Tiktopulo El, Bychkova VE, Ricka J, Ptitsyn OB. Cooperativity of the Coil-Globule Transition in a Homopolymer:Microcalorimetric Study of Poly(N-isopropylacrylamide). Macromolecules.1994,27:2879-2882
[154]Han CK, Bae YH. Inverse thermally-reversible gelation of aqueous N-isopropylacrylamide copolymer solutions. Polymer.1998,39:2809-2814
[155]Bokias G, Staikos G, Iliopoulos I. Solution properties and phase behavior of copolymers of acrylic acid with N-isopropylacrylamide:the importance of the intrachain hydrogen bonding. Polymer.2000,41:7399-7405
[156]Kusonwieiyawong E, Wetering P, Hubbell JA, Merkle IIP, Walter E. Evaluation of pH-dependent membrane-disruptive properties of poly(acrylic acid) derived polymers. European Journal of Pharmaceutics and Biopharmaceutics.2003,56:237-246
[157]Amalvy JI, Wanless EJ, Michailidou YLY, Armes SP. Synthesis and Characterization of Novel pH-Responsive Microgels Based on Tertiary Amine Methacrylates. Langmuir.2004, 20:8992-8999
[158]Schimdt S, Motachmann H, Hwllweg T, Klitzing RV. Thermoresponsive surfaces by spin-coating of PNIPAM-co-PAA microgels:A combined AFM and ellipsometry study. Polymer.2008,49:749-756
[159]Zakir MR, Dincer S, Piskin E. Functional copolymers of N-isopropylacrylamide for bioengineering applications. Prog Polym Sci.2007,32:534-595
[160]Woodle MC, Papahadjopoulos D. Liposome preparation and size characterization. Methods in Enzymology.1989,171:193-217
[161]Inomata H, Goto S, Otake K, Saito S. Effect of additives on phase transition of N-isopropylacrylamide gels. Langmuir.1992,8:687-690
[162]Zignani M, Drummond DC, Meyer O, Hong K, Leroux J-C. In vitro characterization of a novel polymeric-based pH-sensitive liposome system. Biochimica et Biophysica Acta. 2000,1463:383-394
[163]Ni CH, Zhu XX, Wang QL, Zeng XY. Studies on LCST of poly(N-isopropylacrylamide-co-acrylic acid-co-N-diacetone acrylamide). Chinese Chemical Letters.2007,18:79-80
[164]Wei H, Zhang XZ, Cheng C, Cheng SX, Zhuo RX. Self-assembled thermoresponsive micelles of poly(N-isopropylacrylamide-b-methyl methacrylate). Biomaterials.2006,27: 2028-2034
[165]Yessine MA, Lafleur M, Meier C, Petereit HU, Leroux JC. Characterization of the membrane-destabilizing properties of different pH-sensitive methacrylic acid copolymers. Biochimica et Biophysica Acta.2003,1613:28-38
[166]Zhang JP, Wang AQ. pH- and thermo-responsive dispersion of single-walled carbon nanotubes modified with poly(N-isopropylacrylamide-co-acrylic acid). Journal of Colloid and Interface Science.2009,334:212-216
[167]Fei JQ, GU LX. PVA/PAA thermo-crosslinking hydrogel fiber:preparation and pH-sensitive properties in electrolyte solution. Europen Polymer Journal.2002,38: 1653-1658
[168]Yang XY, Chen LT, Huang B, Bai F, Yang XL. Synthesis of pH-sensitive hollow polymer microspheres and their application as drug carriers. Polymer.2009,50:3556-3563
[169]YuXi Z, FeiPeng W, MiaoZhen L, ErJian W. pH switching on-off semi-IPN hydrogel based on cross-linked poly(acrylamide-co-acrylic acid) and linear polyallyamine. Polymer. 2005,46:7695-7700
[170]Jamie O, Mona P, Anthony L, Dan N. Controlling the collapse/swelling transition in charged hydrogels. Biomaterials.2004,25:4345-4353
[171]Dayananda K, He C, Dong KP, Tae GP, Lee DS. pH- and temperature-sensitive multiblock copolymer hydrogels composed of poly(ethylene glycol) and poly(amino urethane). Polymer.2008,49:4968-4973
[172]Dayananda K, He C, Lee DS. In situ gelling aqueous solutions of pH- and temperature-sensitive poly(ester amino urethane)s. Polymer.2008,49:4620-4625
[173]Jian F, Honglai L, Ying H. Micro-phase separation of diblock copolymer in a nanosphere:Dissipative particle dynamics approach. Fluid Phase Equilibria.2007,261:50-57
[174]Xu H, Honglai L, Ying H. Dynamic density functional theory based on equation of state. Chemical Engineering Science.2007,62:3494-3501
[175]纪朝红,葛红江.调剖堵水材料研究现状与发展趋势.石油钻采工艺.2002,24(1):54-57
[176]史向阳,吴世康,孙曹民.疏水化修饰的聚N-异丙基丙烯酰胺高分子的水溶液性质研究.高分子学报.1999,2:16-25
[177]Taillefer J, Jones MC, Brasseur N, Van LJE, Leroux JC. Preparation and characterization of ph-responsive polymeric micelles for the delivery of photosensitizing anticancer drugs. Journal of Pharmaceutical Sciences.2000,89:52-62
[178]Roux E, Francis M, winnik FM, Leroux JC. Polymer based pH-sensitive carriers as a means to improve the cytoplasimic delivery of drug. International Journal of Pharmaceutics. 2002,242:25-36
[179]Gehrke S.H., Palasis M, Akhtar M.K. Effect of synthesis conditions on properties of poly(N-isopropylacrylamide) gels. Polymer International.1992,29:29-36
[180]Antonios K, Tian T, Vasiliki H, Kyriakos V, Lan WH. Micellar and surface properties of a poly(methyl methacrylate)-block-poly(N-isopropylacrylamide) copolymer in aqueous solution. Journal of Colloid and Interface Science.2008,320:70-73
[181]Shi XY, Wang SK. Water Solution Properties of Hydrophobically Modified Poly(N-isopropylacrylamides). Acta Polymerica Sinica.1999,2:16-23
[182]Cheon JB, Jeong Y, Cho CS. Effects of temperature on diblock copolymer micelle composed of poly(γ-benzyl -glutamate) and poly(N-isopropylacrylamide). Polymer.1999, 40:2041-2050
[183]Zhang W, Dong GJ, Yang H, Sun JH, Zhou JZ, Wang JB. Synthesis, surface and aggregation properties of a series of amphiphilic dendritic copolymers. Colloids and Surfaces A:Physicochem Eng Aspects.2009,348:45-48
[184]Fraaije JGEM, Vlimmeren BAC, Maurits MN, Postma M, Evers OA, Hoffman C, Altevogt P. The dynamics mean-field density functional method and its appliation to mesoscopic dynamics of quenched block copolymer melts. Journal of Chemical Physics.1997, 104:4260-4269
[185]Groot RD, Warren P. Dissipative Particle Dynamics:Bridging the gap between atomistic ans mesoscopic simulation. J Chem Phys.1997,107:4423-4435
[186]GAO C, Moehwald H, Shen J. Thermosensitive poly(allylamine)-g-poly(N-isopropylacrylamide):synthesis, phase separation and particle formation. Polymer.2005,46:4088-4097
[187]Wang LQ, Tu KH, Li YP, Zhang J. Phase Transtion and Micellization of Temperature Responsive Dextran-graft-poly(N-isopropylacrylamide) Polymers. Chinese Chemical Letters. 2003,14:407-410
[188]O'Lenick TG, Jiang XG, Zhao B. Thermosensitive Aqueous Gels with Tunable Sol-Gel Transition Temperatures from Thermo- and pH-Responsive Hydrophilic ABA Triblock Copolymer. Langmuir.2010,26:8787-8796
[189]Gan LH, Cai W, Tam KC. Sudies of phase transition of aqueous solution of poly(N,N-diethylacrylamide-co-acrylic acid) by differerntial scanning calorimetry and specrophotometry. European Polymer Journal 2001,37:1773-1778
[190]Herman F, You HB, Jan F, Sung WK. Effect of comonomer Hydrophilicity and ionization on the lower critical solution temperature of N-isopropylacrylamide copolymers. Macromolecules.1993,26:2496-2500
[191]Roux E, Lafleur M, Lataste E, Moreau P, Leroux JC. On the characterization of pH-sensitive liposome/polymer complexes. Biomacromolecules.2003,4:240-248
[192]Feil H, Bae YH, Feijen J, Kim SW. Effect of comonomer hydrophilicity and ionization on the lower critical solution temperature of N-isopropylacrylamide copolymers. Macromolecules.1993,26:2496-2500
[193]Vemuri S, Rhodes CT. Preparation and characterization of liposomes as therapeutic delivery systems:a review Pharmaceutica Acta Helvetiae.1995,70:95-111
[194]Schuch H, Klingler J, Rossmanith P, Frechen T, Gerst M, Feldthusen J, Muller AHE. Characterization of micelles of polyisobutylene-block-poly(methacrylic acid) in Aqueous Medium. Macromolecules.2000,33:1734-1740
[195]Zhou WT, An XQ, Gong J, Shen WG, Chen ZY, Wang XY Synthesis, characteristics and phase behaviour of a thermosensitive and pH-sensitive polyelectrolyte. Journal of applied polymer science.2011,121:2089-2037
[196]Gao C, Mohwald H, Shen J. Thermosensitive poly(allylamine)-g-poly(N-isopropylacrylamide):synthesis, phase separation and paricel formation. Polymer.2005,46:4088-4097
[197]Liu S, Weaver J, Save M, Armes S. Synthesis of pH-responsive shell cross-linked micelles and their use as nanoreactors for the preparation of gold nonoparticles. Langmuir. 2002,18:8350-8357
[198]Cho EC, Lim HJ, Kim HJ, Son ED, Choi HJ, Park JH, Kim JW, Kim J. Role of pH-sensitive polymer-liposome complex in enhancing cellular uptake of biologically active drugs. Materials Science and Engineering C.2009,29:774-778
[199]Asgharian N, Schelly ZA. Electric field-induced transient birefringence and light scattering of synthetic liposomes Biochimica et Biophysica Acta.1999,1418:295-306
[200]Kono K, Hayashi H, Takagishi T. Temperature-sensitive liposomes:liposomes bearing poly (N-isopropylacrylamide) Journal of Controlled Release.1994,30:69-75
[201]Kim JC, Kim JD. Release property of temperature-sensitive liposome containing poly(N-isopropylacrylamide). Colloids and Surfaces B:Biointerfaces.2002,24:45-52
[202]Paoli EE, Kruse D, Seo JW, Zhang H, Kheirolomoom A, Watson KD, Chiu P, Stahlberg H, Ferrara KW. An optical and microPET assessment of thermally-sensitive liposome biodistribution in the Met-1 tumor model:Importance of formulation. Journal of Controlled Release.2010,143:13-22
[203]Kono K, Yoshino K, Takagishi T. Effect of poly(ethylene glycol) grafts on temperature-sensitivity of thermosensitive polymer-modified liposomes. Journal of Controlled Release.2002,80:321-332
[204]Viroonchatapan E, Sato H, Ueno M, Adachi I, Tazawa K, Horikoshi I. Magnetic targeting of thermosensittve magnetoliposomes to mouse livers in an in situ on-line perfusion system. Life Sciences.1996,58:2251-2261
[205]Dandamudi S, Campbell RB. Development and characterization of magnetic cationic liposomes for targeting tumor microvasculature. Biochimica et Biophysica Acta.2007,1768: 427-438
[206]Nakao R, Matuo Y, Mishima F, Taguchi T, Maenosono S, Nishijima S. Development of magnetic separation system of magnetoliposomes. Physica C:Superconductivity.2009,469: 1840-1844
[207]Wardak A, Brodowski R, Krupa Z, Gruszecki WI. Effect of light-harvesting complex II on ion transport across model lipid membranes Journal of Photochemistry and Photobiology B:Biology.2000,56:12-18
[208]Christina RM, Paula JC, David FO. Visible light-induced destabilization of endocytosed liposomes. FEBS Letters.2000,467:52-56
[209]Turk MJ, Reddy JA, Chmielewski JA, Low PS. Characterization of a novel pH-sensitive peptide that enhances drug release from folate-targeted liposomes at endosomal pHs Biochimica et Biophysica Acta.2002,1559:56-68
[210]Maitani Y, Igarashi S, Sato M, Hattori Y. Cationic liposome (DC-Chol/DOPE=1:2) and a modified ethanol injection method to prepare liposomes, increased gene expression. International Journal of Pharmaceutics.2007,342:33-39
[211]Ding WX, Qi XR, Li P, Maitani Y, Nagai T. Cholesteryl hemisuccinate as a membrane stabilizer in dipalmitoylphosphatidylcholine liposomes containing saikosaponin-d. International Journal of Pharmaceutics.2005,300:38-47
[212]Lai MZ, Vail JW, Szoka FC. Acid- and Calcium-Induced Structural Changes in Phosphatidylethanolamine Membranes Stabilized by Cholesteryl Hemisuccinatet. Biochemistry.1985,24:1654-1661
[213]Zhao XB, Lee RJ. Tumor-selective targeted delivery of genes and antisense oligodeoxyribonucleotides via the folate receptor Advanced Drug Delivery Reviews.2004,56: 1193-1204
[214]Fonseca C, Moreira JN, Ciudad CJ, Pedroso MC, Simoes S. Targeting of sterically stabilised pH-sensitive liposomes to human T-leukaemia cells European Journal of Pharmaceutics and Biopharmaceutics.2005,59:359-366
[215]Suzuki S, Watanabe S, Masuko T, Hashimoto Y. Preparation of long-circulating immunoliposomes containing adriamycin by a novel method to coat immunoliposomes with poly(ethylene glycol) Biochimicaet Biophysica Acta.1995,1245:9-16
[216]Zeng XJ, Zeng XH. Relationship between the clinical effects of berberine on severe congestive heart failure and its concentration in plasma studied by HPLC. Biomedical Chromatograhy.1999,13 (7):442-444
[217]R.G Kinga, R.M. Marchbanks. The effect of pH on the size of liposomes formed by cholate dialysis. Biochimica et Biophysica Acta.1982,691:183-187
[218]Kono K, Henmi A, Yamashita H, Hayashi H, Takagishi T. Improvement of temperature-sensitivity of poly(N-isopropylacrylamide)-modified liposomes. Journal of Controlled Release.1999,59:63-75
[219]Mikes V, Kovar J. Interaction of liposomes with homologous series of fluorescent berberine derivatives:New cationic probes for measuring membrane potential Biochimica et Biophysica Acta (BBA)-Biomembranes.1981,640:341-351
[220]Fueldner HH. Characterization of a third phase transition in multilamellar dipalmitoyllecithin liposomes. Biochemistry.1981,20:5707-5710
[221]Lewis BA, Das Gupta SK, Griffin RG. Solid-state NMR studies of the molecular dynamics and phase behavior of mixed-chain phosphatidylcholines. Biochemistry.1984,23: 1988-1993
[222]Takeuchi H, Yamamoto H, Toyoda T. Physical stability of size controlled small unilameller liposomes coated with a modified polyvinyl alcohol. International Journal of Pharmaceutics.1998,164:103-111
[223]MC W. Controlling liposome blood clearance by surface-grafted polymers. Advanced Drug Delivery Reciews.1998,32:139-152
[224]Yang X, Lee HY, You SG, Kim JC. pH- and temperature-dependent release from cationic vesicles coexisting with copolymer of N-isopropylacrylamide and methacrylic acid. Colloids and Surfaces A:Physicochemical and Engineering Aspects.2009,348:109-115
[225]Ringsdorf H, Sackmann E,Simon J, Winnik FM. Interactions of liposomes and hydrophobically-modified poly-(N-isopropylacrylamides):an attempt to model the cytoskeleton. Biochimica et Biophysica Acta (BBA)-Biomembranes.1993,1153:335-344
[226]An XQ, Zhang F, Zhu YY, Shen WG. Photoinduced drug release from thermosensitive AuNPs-liposome using a AuNPs-switch. Chem Commun.2010,46:7202-7204
[227]Kono K, Hayashi H, Takagishi T. Temperature-sensitive liposomes:liposomes bearing poly (N-isopropylacrylamide). Journal of Controlled Release.1994,30:69-75
[228]Makino K, Yamada T, Kimura M, Oka T, Ohshima H, Kondo T. Temperature-and ionic strength-induced conformational changes in the lipid head group region of liposomes as suggested by zeta potential data Biophys Chem 1991,41:175-183
[229]Sabin J, Ruso JM, Gonzalez-Perez A, Prieto G, Sarmiento F. Characterization of phospholipid+semifluorinated alkane vesicle system. Colloids and Surfaces B:Biointerfaces. 2006,47:64-70