奥沙利铂几种新型脂质体的制备及对大肠癌靶向性与药动学研究
|
摘要
奥沙利铂是一种治疗大肠癌的新药,但其毒副作用较大,并发症较多,靶向性不强,使其对大肠癌的治疗受到限制。
研究目的:以脂质体为药物载体,以大肠靶向、低毒与缓释为目标,以奥沙利铂(Oxaliplatin)为模型药物,系统研究常规脂质体、长循环脂质体、长循环热敏脂质体和长循环免疫脂质体的处方、制备工艺、性质、靶向性和药动学规律。方法:以脂质体的包封率为指标综合评价,采用正交设计对制备工艺进行优化,用反相蒸发超声法制得奥沙利铂脂质体。同法制得奥沙利铂长循环脂质体、长循环热敏脂质体、长循环免疫脂质体。采用纳米粒径仪、高效液相色谱仪等检测其形态、粒径、含量等。结果:在选定波长下高液色相色谱中各辅料、组织、血清中的物质对奥沙利铂的检测无干扰。奥沙利铂常规脂质体其最佳制备工艺为磷脂浓度为40mg·ml~(-1),药脂比为1:40,超声时间为6min,磷脂与胆固醇比为4:1,其平均包封率为85.46%±2.31%。平均粒径为空白脂质体69.4nm,常规脂质体9.3nm。奥沙利铂长循环脂质体为108.1nm,12h的累积释放量不足10%。奥沙利铂长循环热敏脂质体的包封率为85.24%,粒径为118.2nm。在42℃加热30min时,药物释放率89.4%达到最高值。奥沙利铂长循环免疫脂质体的粒径为130.9nm,包封率为85.17%。奥沙利铂长循环免疫脂质体的靶向效率为57.3%,是奥沙利铂长循环热敏脂质体的1.3倍,奥沙利铂长循环脂质体的4.6倍。结论:奥沙利铂几种新型脂质体的制备条件可行易工业化,产品稳定性较好,大肠靶向性增强,肾毒性降低,达到了本课题的预期目标。
Oxaliplatin is a common drug for colon cancer with limited application because of strong adverse reaction,many complications and inferior targeting.
Objective:To research common,long-circulating,long circulating thermosensitive, long circulating immunoliposomes about their formulas,preparation technology,characters,targeting and pharmacokinetics regularity with liposome as a carrier,Oxaliplatin as a model drug and target of colon targeting,low toxicity and delayed release.Methods:The enbedding ratio as an index was evaluated to the optimizing preparation technology with an orthogonal design.Oxaliplatin common liposome was prepared with reverse phase evaporation.Oxaliplatin long-circulating, long circulating thermosensitive and long circulating immunoliposomes were prepared with the same method.Their shapes,sizes,concents etc.were detected with nanosizer and HPLC.Results:Materials in preparation,tissues and serum did not trouble the detection of Oxaliplatin in HPLC at 250nm.The optimal preparation technology of Oxaliplatin common liposome was 40 mg·ml~(-1) phospholipids,drug: phospholipids as 1:40,taking ultrasound for 6 min,phospholipids:cholesterol as 4:1 and with mean enbedding ratio as(85.46%±2.31%).The mean size was 69.4 nm for Blank liposome,79.3 nm for common liposome.Accumulated release during 12 hours was＜10%for Oxaliplatin long-circulating liposome with 108.1 nm size.Oxaliplatin long-circulating thermosensitive lipsome was with 85.24%embedding ratio,118.2 nm size and 89.4%drug release as a peak when heating 30 min at 42℃.Targeting efficiency of Oxaliplatin long circulating immunoliposome group with 57.3%(Te) was 1.3 times of that of Oxaliplatin long circulating thermosensetive liposome group, and 4.6 times of that of Oxaliplatin long-circulating liposome group.Its concentrations in serum,lung,kidney and heart were lower than those in free drug group.Conclusions:Oxaliplatin complex liposome was easy for industry,stabile well, could increase markedly the targeting in colon,decrease kidney toxicity and reached objective of this research.
研究目的:以脂质体为药物载体,以大肠靶向、低毒与缓释为目标,以奥沙利铂(Oxaliplatin)为模型药物,系统研究常规脂质体、长循环脂质体、长循环热敏脂质体和长循环免疫脂质体的处方、制备工艺、性质、靶向性和药动学规律。方法:以脂质体的包封率为指标综合评价,采用正交设计对制备工艺进行优化,用反相蒸发超声法制得奥沙利铂脂质体。同法制得奥沙利铂长循环脂质体、长循环热敏脂质体、长循环免疫脂质体。采用纳米粒径仪、高效液相色谱仪等检测其形态、粒径、含量等。结果:在选定波长下高液色相色谱中各辅料、组织、血清中的物质对奥沙利铂的检测无干扰。奥沙利铂常规脂质体其最佳制备工艺为磷脂浓度为40mg·ml~(-1),药脂比为1:40,超声时间为6min,磷脂与胆固醇比为4:1,其平均包封率为85.46%±2.31%。平均粒径为空白脂质体69.4nm,常规脂质体9.3nm。奥沙利铂长循环脂质体为108.1nm,12h的累积释放量不足10%。奥沙利铂长循环热敏脂质体的包封率为85.24%,粒径为118.2nm。在42℃加热30min时,药物释放率89.4%达到最高值。奥沙利铂长循环免疫脂质体的粒径为130.9nm,包封率为85.17%。奥沙利铂长循环免疫脂质体的靶向效率为57.3%,是奥沙利铂长循环热敏脂质体的1.3倍,奥沙利铂长循环脂质体的4.6倍。结论:奥沙利铂几种新型脂质体的制备条件可行易工业化,产品稳定性较好,大肠靶向性增强,肾毒性降低,达到了本课题的预期目标。
Oxaliplatin is a common drug for colon cancer with limited application because of strong adverse reaction,many complications and inferior targeting.
Objective:To research common,long-circulating,long circulating thermosensitive, long circulating immunoliposomes about their formulas,preparation technology,characters,targeting and pharmacokinetics regularity with liposome as a carrier,Oxaliplatin as a model drug and target of colon targeting,low toxicity and delayed release.Methods:The enbedding ratio as an index was evaluated to the optimizing preparation technology with an orthogonal design.Oxaliplatin common liposome was prepared with reverse phase evaporation.Oxaliplatin long-circulating, long circulating thermosensitive and long circulating immunoliposomes were prepared with the same method.Their shapes,sizes,concents etc.were detected with nanosizer and HPLC.Results:Materials in preparation,tissues and serum did not trouble the detection of Oxaliplatin in HPLC at 250nm.The optimal preparation technology of Oxaliplatin common liposome was 40 mg·ml~(-1) phospholipids,drug: phospholipids as 1:40,taking ultrasound for 6 min,phospholipids:cholesterol as 4:1 and with mean enbedding ratio as(85.46%±2.31%).The mean size was 69.4 nm for Blank liposome,79.3 nm for common liposome.Accumulated release during 12 hours was＜10%for Oxaliplatin long-circulating liposome with 108.1 nm size.Oxaliplatin long-circulating thermosensitive lipsome was with 85.24%embedding ratio,118.2 nm size and 89.4%drug release as a peak when heating 30 min at 42℃.Targeting efficiency of Oxaliplatin long circulating immunoliposome group with 57.3%(Te) was 1.3 times of that of Oxaliplatin long circulating thermosensetive liposome group, and 4.6 times of that of Oxaliplatin long-circulating liposome group.Its concentrations in serum,lung,kidney and heart were lower than those in free drug group.Conclusions:Oxaliplatin complex liposome was easy for industry,stabile well, could increase markedly the targeting in colon,decrease kidney toxicity and reached objective of this research.
引文
[1]Martin C Woodle,Danilo D Lasic Sterically Stabilized Liposomes [J].Biochimica Biophysica Acts,1992,1113:171-199
[2]陈伟,雷连成,韩文瑜,等利福平脂质体制备工艺的初步研究中国兽药杂志,2002,36(4):24-26
[3]赵荣生,侯新朴,严定霞两性霉素B脂质体的制备及稳定性研究 中国医药工业杂志,2001,32(40:160-162)
[4]王健松,朱家壁 阿奇霉素脂质体的制备及包封率测定 中国药科大学学报,2004,35(6):499-502
[5]穆筱梅,钟振声,陈焕钦果酸脂质体的制备、检测及应用 香料香精化妆品,2002,10(5):25-27
[6]龚金红,刘扬,唐丽华,等盐酸利多卡因脂质体凝胶剂的制备及经皮渗透动力学中国药学杂志,2005,40(11):839-842
[7]五学清,齐宪荣,刘明辉盐酸丁卡因脂质体凝胶剂的制备与释放度的测定中国现代应用药学杂志,2003,20(1):37-40
[8]Rouzi B.Retorolac tromethamine liposome:encapsulation and release studies.J Liposome Res,2005,15(31):175-185.
[9]徐丽君,陆付耳,魏世超等 盐酸小檗碱脂质体的制备方法及质量研究 中国医药药学杂志,2004,24(16):325-326
[10]李维风,牛晓峰,陈海英等PH-梯度-冻融法制备硝苯地平脂质体西安交通大学学报(医学版),2003,24(6):578-580
[11]叶志伟,胡乔红,梁文权粉末床研磨法制备干扰素-脂质体 浙江大学学报(医学版),2002,31(6):433-436
[12]Khuller GK,Kapui M,Sharma S.Liposome technology for drag delivery anainst mycobaterial infections.Curr Pharma Design,2004,10(26):3263-3274.
[13]邓意辉,李焕秋,王绍宁,等主动载药与被动载药制备盐酸左氧氟沙星脂质体 中国抗生素杂志,2001,26(4):40-42
[14]邓意辉,王绍宁,吴琼,等.主动载药法制备盐酸小檗碱脂质体.中国药学杂志,2004,38(1):40-42
[15]杜松,邓英杰,张威.主动载药法制备盐酸去氢骆驼蓬碱脂质体.中草药,2005,36(5):673-676
[16]Allen T M chona,A Large unilia mellar liposomes with low uptake into the reticuliendothelial system[J].FEBS Lett:1987,223:42-46.
[17]赵海霞,郭兴奎,孙德亮,田景振.脂质体制备技术[J].山东中医杂志,2000,19(7):435-437.
[18]顾学裘,马竹卿,辛顺妹等抗癌药新剂型—多相脂质体的研究(Ⅱ)多相脂质体(139,76)混悬液静脉注射液的左究。中划药,1982:13(5):15-20.
[19]Kremer J M H,Vesicles of various diameters by a modified injection method[J].biochemistry,1977,16(17):3932-3935.
[20]阎家麒,童岩,王九一紫杉醇脂质体的制备及其抗瘤的研究[J]药物生物技术,1996,3(3):1-5
[21]李国峰,周日红,曾抗等维生素E脂质体的制备[J]中国应用药学,1997,14(4):18-20
[22]Wang C Y,Yughes K W,Huang L,improved cytoplasmic delivery to plant protoplasts via PH-sensitive liposome[J].Plant ohysiol,1986,82:179-186.
[23]Ropert c,Malvy C,Couvreur P.inhibition if the friend retrovirus by antisense oligonucleotide encapsulatedin liposome[J]mechamism of action,1986,82:179-186.
[24]Szoka F,Olsom F,Preparation of liposome of intermedia size by a combination of reverse phase evaporation and extrusion trough polyamonate membranes[J].Biochm Biophys Acta,1980,601:559-571.
[25]全东琴,苏德林,顾学裘药物载体空白脂质体前体制备及性质的研究[J]沈阳药科大学学报,1999,16(3:160-164.)
[26]GUPTA P K,HUNGC T.Quantitative evaluation of targeted drug delivery systems[J].Int J Pharrn,1989,56(3):217-226.
[27]Crommelin DJA.Liposomes as carries for drus and antiens:approaches to preserve their long term stability[J].Drug Dev Ind Pharm,1994,20(4):547.
[28]Allen TM Long-circuiting(sterically stabilized) liposomes for targeted drug delivery[J]Trends Pharmacol Sci.1994.15(7):215-220
[29]Nagayaso A,Shimooka Y,Kmouchi T,et al Effects of fliodity and vesicle size on antitumor activity and myclosuppressive activity of liposomes loaded with daunorubicin[J].Biol Pharm Bull,1994.17(7):935-939
[30]Nagayasu A.Uchiyama K.Krwada H.The size of liposomes:a factor which affects their targeting efficiency to tumors and therapeutic activity of liposomal antitumor drugs[J]Adv Drug Deliv Rev,1999,40(1):75-87
[31]Yatvin M B,Weinstein J N,Dennie W H,et al.Design of lipomes for enhanced loci release of drugs by hyperthermin[J].Science,1978,202(4374):1290
[32]李建人.高热治疗恶性肿瘤的临床应用[J].国外医学肿瘤学分册,1994,24(4):219.
[33]Chelvi T P,Ralhan R.Hyperthemia potentiates antitumor effect of thermosensitive liposome encapsulated mephalan and radiation in murine melanoma[J].Tumour Biol,1997,18(4):250-260.
[34]Kakinuma K,Tanaka R,Takahushi H,et al.Drug delivery to the brain using thermosensitive liposome and local hyperthermia[J].Int J Hyperthennia,1996,12(1):157-165.
[35]lga K.Ohkouehi K,Ogawa Y,et al.Membrane modification by negatively charged stearyt-polyaxycthylene derivatives for thermosensitive liposomes;reduced liposomal aggregation and avoidance of RES uptake[J].J Drug Target,1994,2(3):259.
[36]Unezaki S,Manuyama K,Takahashi N,et al.Enhanced deliver and antitumor activity of doxorubicin using long-circulating thermosensitive liposomes containing amphipathic polyethylene glycol in combination with local bypenhermia[J].Pharm Res,1994,1(8):1180.
[37]Gaber M H,Hong K,Huang S K,et al.Thermosenstitive sterically stabilized liposomes;formulation and in vitro studies on mechanism of doxorubicin release in bovine serum and human plasma[J].Pharm Res,1995,12(10):1407.
[38]叶伟民,韩焕兴,范列英,等.Bradford比色法简便、快速测定微量蛋白[J].上海医学检验杂志,1996,11(4):207-208
[39]陆斌.免疫分子敏感膜的组装技术研究[D].南京:东南大学,1999.
[40]杨镇.肿瘤免疫学[M].武汉:湖北科学出版社,1998.Nam S M,Kim H S,Ahn W S,et al.Sterically stabilized anti-G(M3),anti-Le(x) immunoliposomes:targeting to B16BL6,HRT-18 cancer cells[J].Oncol Res,1999;11:9-16.
[41]Koning G A,Morselt H W,Velinova M J,et al.Selective transfer of a lipophilic prodrug of 5-fluorodeoxyuridine from immunoliposomes to colon cancer cells[J].Biochim Biophys Acta,2003;1420:153-167.
[1]Okayama R,Noji M,Nakanishi M.Cationic cholesterol with a hydmxyethylamino head group promotes significantly liposome mediated gene transfection.FEBS Lett,1997,408(2):232
[2]Juliano RL,Akhtar S.Liposome as a drug delivery system for antisense oligonucleotides.Antisense Res Dev,1992,2(1):165
[3]Ropert C,Lavignon M,Dubemet C,et al.Oligonucliotides encapsulated in pH sensitive liposomes are efficient toward friend retrovirus.Biochem Biophys Res Commun,1992,183(2):879
[4]Ropert C,Malvy C,Couvreur P.Inhibition of the friend retrovirus by antisense oligonucleotide encapsulated in liposome:mechanism of action.Pharma Res,1993,10(10):1427
[5]Tari AM,Tucker SD,Deisseroth A,et al.Liposome delivery of methyphosphonate antisense oligodeoxynucleotide in chronic myelogenous leukemia.Blood,1994,84(2):601
[6]Lasic DD,Templeton NS.Liposomes in Gene Therapy Adv Drug DelR ev,1996,20(2,3):221
[7]Scan M,Sullivan.Liposome based gene transfer vehicles.Biopharm,1996,50-51:65
[8]Wu XF,Lee KH,Li QT.Stability and pH sensitivity of sulfatide-containing phosphatidylethanolamine small unilamellar vesicles. Biochim Biophy Acta,1996, 1284(1): 13
[9] Jeong MH, Lee YS, Jin JY, et al. pH Sensitive liposomes containing a bipolaramphiphile as a protonatable component. Bull Korean Chem Soc, 1996,17(10): 875
[10] Dzau VJ, Mann MJ, Morishita R, et al. Fusigenic viral liposome for gene therapy in cardiovascular diseases. Proc Natl Acad Sci USA, 1996, 93(21): 11421
[11] Geisert EE, Mar NAD, Owens JL, et al. Transfecting neurons and glia in the rat using pHsensitive immunoliposomes. Neurosci Lett, 1995,184(1): 40
[12] Ma DDF, Wei AQ.Enhanced delivery of synthetic oligonucleotides to human leukemic cells by liposomes and immunoliposomes. Leuk Res, 1996, 20(11/12):925
[13] Slepushkin VA, Simoes S, Dazin P, et al. Sterically stabilized pH sensitive liposomes. Intracellular delivery of aqueous contents and prolonged circulation in vivo. J Biol chem, 1997, 272(4): 2382
[14] Kono K, Igawa T, Takagishi T. Cytoplasmic delivery calcein mediated by liposomes modified with a pH sensitive poly(ethyleneglycol) derivative.Biochim Biophy Acta, 1997,1325(2): 143
[15]Morais P C, Santos J G, Neto K S, et al. Magnetic resonance of magnetic fluid and magnetoliposome preparations. J Magn Magn Mater, 2005, 293: 526
[16] Giri J, Thakurta S G, Bellare J, et al. Preparation and characterization of phospholipid stabilized uniform sized magnetite nanoparticles. J Magn Magn Mater, 2005, 293: 62
[17] Martina M S, Fortin J P, Menager C, et al. Generation Of Superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging. J Am Chem Soc, 2005, 127: 10676
[18] Park J, An K, Hwang Y, et al. Ultra-large-scale syntheses of monodisperse nanocrystals. Nature Mater, 2004, 3: 891
[19] Wang Xun, Zhuang Jing, Peng Qing, et al. A general strategy for nanocrystal synthesis. Nature, 2005, 437: 121
[20] Cuyper M D, PM uller, Lueken H, et al. Synthesis of magnetic Fe3O4 particles covered with a modifiable phospholipids coat. J Phys: Condens Mater, 2003,15: S1425
[21] Kuznetsov A A, Filippo V I, Alyautdin R N, et al. Application of magnetic liposomes for magnetically guided transport of muscle relaxants and anticancer photodynamic drugs. J Magn Magn Mater, 2001, 225: 95
[22]Nawroth T, Rusp M , M ay R P. Magnetic liposomes and entrapping :time-resolved neutron scattering TR-SANS and electron microscopy. Physica B,2004, 350: e635
[23]Jain S, Mishra V, Singh P, et al. ROD-anchored magnetic liposomes for monocytes / neutrophils-mediated brain targeting. Int J Pharmaceutics, 2003,261: 43
[24]Ito K, Shinkai M, Honda H, et al. Medical application of functionalized magnetic nanoparticles. J Biosci Bioeng, 2005, 100(1): 1
[25] Hodenius M, Cuyper M D, Desender I, et al. Biotinylated stealth magnetoliposomes. Chem Phys Lipids, 2002,120: 75
[26]Dominno J C, Mercadal M, Petriz J, et al. Preparation of PPG-grafted immunomannetoliposomes entrapping citrate stabilized mannetite particles and their application in CD34+cell sorting. J Microencapsulation, 2001,18(1):41
[27] Dumitrascu G, Kumbhar A, Zhou W L, et al. The use of derivatized magnetoliposomes for extraction of antibodies from aqueous solutions. IEEE Trans Magnetics, 2001, 37(4): 2932.
[28] Zhang J Q, Zhang Z R, Yang H, et al. Lyophilized paclitaxel magnetoliposomes as a potential drug delivery system for breast carcinoma via parenteral administration: in vitro and in vivo studied. Pharmaceutical Res, 2005,22(4):573.
[29] Kullberg M, Mann K, Owens J L. Improved drug delivery to cancer cells: a method using magnetoliposomes that target epidermal growth factor receptors.Medical Hypotheses, 2005, 64:468.
[30] Hamaguchi S, Tohnai I, Ito A, et al. Selective hyperthermia using magnetoliposomes to target cervical lymph node metastasis in a rabbit tongue tumor model. Cancer Sci, 2003,94(9):834.
[31] Kawai N, Ito A, Nakahara Y, et al. Anticancer effect of hyperthermia on prostate cancer mediated by magnetite cationic liposomes and immune response induction in transplanted syngeneic rats. The Prostate, 2005, 64: 373.
[32] Ito A, Shinkai M, Honda H, et al. Heat shock protein 70 expression induces antitumor immunity during intracellular hyperthermia using magnetite nanoparticles. Cancer Immunol Immunother, 2003, 52:80.
[33] Matsuoka F, Shinkai M, Honda H, et al. Hyperthermia using magnetite cationic liposomes for hamster osteosarcoma. Biomagnetic Res Techn, 2004,2:3.
[34] Yatvin M B, Weinstein J N, Dennie W H, et al. Design of lipomes for enhanced locl release of drugs by hyperthermin [J]. Science, 1978, 202(4374): 1290.
[35]李建人.高热治疗恶性肿瘤的的临床应用[J].国外医学肿瘤学分册, 1994,24(4):219.
[36] Chelvi T P, Ralhan R. Hyperthemia potentiates antitumor effect of thermo-sensitive liposome encapsulated mephalan and radiation in murine melanoma [J].Tumour Biol, 1997, 18(4): 250-260.
[37] Kakinuma K, Tanaka R, Takahushi H, et al. Drug delivery to the brain using thermosensitive liposome and local hyperthermia [J]. Int J Hyperthermia, 1996,12(1): 157-165.
[38] lga K. Ohkouehi K, Ogawa Y, et al. Membrane modification by negatively charged stearyt-polyaxycthylene derivatives for thermosensitive liposomes;reduced liposomal aggregation and avoidance of RES uptake [J]. J Drug Target,1994,2(3):259.
[39] Unezaki S, Manuyama K, Takahashi N, et al. Enhanced deliver and antitumor activity of doxorubicin using long-circulating thermosensitive liposomes containing amphipathic polyethylene glycol in combination with local bypenhermia [J]. Pharm Res, 1994,1(8): 1180.
[40] Gaber M H, Hong K, Huang S K, et al. Thermosenstitive sterically stabilized liposomes; formulation and in vitro studies on mechanism of doxorubicin release in bovine serum and human p lasma [J]. Pharm Res, 1995, 12(10):1407.
[41] Vitoonchatapan E, Sato H, Vero M, et al. Megnetie targeting of thermosensitive magnetoliposomes to mouse livers in an in situ on line perfusion system [J]. Life Sci, 1996, 58 (24): 2251.
[42] Sullivan S M. Huang L. Preparation and characterization of heat sensitive immunoliposome [J]. Biochim Biophys Acta, 1985, 816(1):116.
[43] Schild H G, Tirrell D A. Microscalorimetric detection of lever critical solution temperature in quenous polymer solution [J]. J Phys Chem, 1990, 94 (1):4352-4356.
[44] Kim J C, BaeSoo K, Kim J D. Temperature-sensitivity of liposomal lipid bilayers mixed with poly(N-isopropylacry lamide)-co-acrylic acid [J]. J Biochem, 1997, 121(1):15-19.
[45]Hayashi H,Kono K,Takagishi T.Temperature-controlled release property of phospholipids vesicles beating a thermosensitive polymer[J].Biochem Biophys Acta,1996,1280(1):127-134.
[46]赵峰等,天然大豆磷脂制备热敏脂质体的方法及质量评价[J].中国天然药物,2005,3(4):7.
[47]邢同京.免疫脂质体研究进展[J].国外医学预防、诊断、治疗用生物制品分册,2002,(21):214-217.
[48]陆斌.免疫分子敏感膜的组装技术研究[D].南京:东南大学,1999.
[49]徐梁,张学庸,莫简.胃癌特异性免疫脂质体的制备及其体内外抗肿瘤作用[J].第四军医大学学报,2002,(12):68-72.
[50]Truneh A,Machy P,Horan P K,et al.Antibody bearing liposomesas multicolor immunofluorescence markers for flowcytometry and imaging[J].JImmunol-Methods,1987,100:59-65.
[51]Sriwongsitanont S,Ueno M.Physicochemical properties of PEG-grafted Liposomes.Chem Pharm Bull,2002,50:1238-1244.
[52]Allen TM,Brandeis E,Hansen CB,et al.A new strategy for attach mentofantibodies to sterically stabilized liposomes resulting in efficient targeting to cancer cells.Biochim Biophys Acta,1995,1237:99-108.
[53]Hawyler J,Yang J,Pardridge WM.Receptor mediated delivery of dannomycin using immunoliposomes:pharmacokineties and tissue distribution in the rat.J Pharmacol Exp Ther,1997,282:1541-1546.
[54]Harding JA,Engbers CM,Newman MS,et al.Immunogenicity and pharmacokinetic attributes of poly(ethyleneglycol)-grafted immunolipsomes.Biochim Biophys Acta,1997,1327:181-192.
[55]Dams ET,Laverman P,Oyen WJ,et al.Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes.J Pharmacol ExpTher,2000,292:1071-1079.
[56]Bendas G,Rothe U,Scherphof GL.et al.The influence of repeated injections on pharmacokinetics and biodistrobution of different types of sterically stabilized immunoliposomes.Biochim Biophys Acta,2003,1069:63-70.
[57]Laverman P,Carstens MG,Boerman OC,et al.Factors affecting the accelerated blood clearance of polyethylene glycol liposomes upon repeated injection.J pharmacol ExpTher,2001,298:607-612.
[58] Goins B, Phillips WT, Klippers R. Repeat injection studies of technetium 99m-labeled PEG-liposomes in some animal. J Liposome Res, 1998, 8: 265-281.
[59] Oussoren C, Storm G. Effect of repeated intravenous administration on the circulation kinetics of poly(ethyleneglycol)-liposomes in cat. J Liposomes Res,1999,9:349-355.
[60] Utkhede DR, Tilcock CP. Effect of lipid dose on the biodistrbution and blood pool clearance kinetics of PEG-modified technetium-labeled lipid vesicles. J Liposomes Res, 1998, 8: 381-390.
[61] Laverman P, Brouwers AH, Dams ET, et al. Preclinical and clinical evidence for disappearance of long-circulating characteristic of polyethyleneglycol liposomes at low lipid dose. J Pharmacol Exp Ther, 2000, 293:996-1001.
[62] YuanF, Dellian M, Fukumura D. Vascular permeability in a human tumor xenograft: molecular size dependence and cut off size. Cancer Res, 1995, 55:3752-3756.
[63] Hobbs SK, Monsky WL, Yuan F. Regulation of transport pathways in tumor vessels: role of tumor type and micro environment. Proc Natl Acad Sci USA,1998,95:4607-4612.
[64] Brown JM, Giaccico AJ. The unique physiology of solid tumors: Opportunities (and problems) for cancer therapy. Cancer Res, 1998, 58: 1408-1416.
[65] Jain RK. Delivery of molecular and cellular medicine to solid tumors. J Control Release, 1998, 53: 49-67.
[66] Allen TM, Ahmad I, Lopes de Menezes DE, et al. Immunoliposomes mediated targeting of anti-cancer drugs in vivo. Biochim SocTrans, 1995, 23: 1073-1079.
[67] Park JW, Hong K, Kirpotin DB, et al. Anti-HER2 immunoliposomes for targeted therapy of human tumors. Cancer Lett, 1997, 118: 153-160.
[68] Lopes de Menezes DE, Pilarski LM, AllenTM. In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-celllymphorma. Cancer Res, 1998,58: 3320-3330.
[69] Koning GA, Morselt HW, Velinova MJ,et al. Selective transfer of a lipophilic prodrug of 5-fluo-rodeoxyuridine from immunoliposomes to colon cancer cells.Biochim Biophys Acta, 1999,1420: 153-167.
[70] Sarti P, Ginohhi P, Agostino ID, et al. HL-60 cells induced by transferic-receptor endocytosis. Biotemich Apl Biochem, 1996,24: 269-276.
[71] Park JW, Hong K, Carter P, et al. Development of anti-p185HER2 immunoliposomes for cancer therapy.Proc Natl Acad Sci USA,1995,92:1327-1331.
[72]Goren D,Horowifz AT,Zalipsky S,et al.Targeting of stealth liposomes to erbB-2(Her/2) receptor in vitro and in vivo studies.Brit J Cancer,1996,74:1749-1756.
[73]LiX,Stuckert P,BoschI,et al.Single-chain antibody-mediated gene delivery into ErbB2-position human breast cancer cells.Cancer Gene Ther,2001,8:555-565.
[74]Park JW,Kirpotin DB,HongK,et al.Tumor targeting using anti-her2immunoliposomes.J Control Release,2001,74:95-113.
[75]Park JW,Hong K,Kirpotin DB,et al.Anti-HER2 immunoliposomes:enhanced efficacy attributable to targeted delivery.Clin Cancer Res,2002,8:1172-1181.
[76]Sugano M,Egilmez NK,Yokota S J,et al.Antibody targeting of doxorubicin-loaded liposomes suppresses the growth and metastatic spread of established human lung tumor xenografts in severe combined immunodeficient mice.Cancer Res.2000,60:6942-6949.
[77]杨镇.肿瘤免疫学[M].武汉:湖北科学出版社,1998.
[78]Nam S M,Kim H S,Ahn W S,et al.Sterically stabilized anti-G(M3),anti-Le(x)immunoliposomes:targeting to B16BL6,HRT-18 cancer cells[J].Oncol Res,1999;11:9-16.
[79]Koning G A,Morselt H W,Velinova M J,et al.Selective transfer of a lipophilic prodrug of 5-fluorodeoxyufidine from immunoliposomes to colon cancer cells[J].Biochim Biophys Acta,2003;1420:153-167.
[80]王华.旋毛虫幼虫单克隆抗体制备和鉴定[J].北京医科大学学报,1988,20(4):285.
[81]徐梁,张学庸,莫简,等.胃癌特异性阿霉素免疫脂质体的制备及其特性[J].中华消化杂志,1999,6:325-328
[82]全东琴,苏德森,顾学裘.由空白脂质体制备抗癌药物脂质体[J].沈阳药科大学学报,1999,16(4):239.
[83]朱盛山 主编.药物新剂型[M].第1版.北京:化学工业出版社,2003:460.
[84]侯新朴,张宇锋,谢蜀生等.第3代载药免疫脂质体及体内外寻靶研究[J].药学学报,2001,36(7):539.
[85]Anne MR,Jonathan EG,Malcolm NL.The specificity and affinity of immunoliposome targeting to oral bacterial[J].Biochim Biophys Acta,1998,1369(2):278.
[86]牛荣丽,薛弘燮,李志良.阿苯达唑免疫脂质体的制备[J].新疆医科大学学报,2001,24(1):60.
[87]王述亘,安国顺,程道新.免疫脂质体作为阿苯达唑载体治疗小鼠泡球蚴病实验研究.[J].寄生虫与医学昆虫学报,1997,4(4):211.
[88]Chuyder A,Huwyler J.Drug transport to brain with targeted liposomes[J].Neuro Rx,2005,2(1):99.
[89]chekhonin VP,Zhirkov IA,Gurina O1.Production and characteristics of PEGylated immunoliposome transport vectors specific for neural tissue astrocytes[J].Biomed Khim,2005,51(3):276.
[90]Huwyler J,Wu D,Pardridge WM.Brain drug delivery of small molecules using immunoliposomes[J].Proc Natl Acac Sci USA,1996,93(24):14164
[91]Shi N,Pardidge WM.Non-invasive gene targeting to the brain[J].Proc Natl Acad Sci USA,2000,97(13):7567.
[92]方瑾,王芸庆,宋今丹紫杉醇免疫脂质体的制备及其对大肠癌的杀伤作用[J].中华微生物学和免疫学杂志,1997,17(1):59.
[93]方瑾,王芸庆,宋今丹.大肠癌免疫脂质体导向紫杉醇的实验研究[J].中国免疫学杂志,1998,14(3):198.
[94]李文锦,钱和年,吕文英,等.免疫脂质体对卵巢癌细胞生长抑制实验的研究[J].北京医科大学学报,1994,25(3):184.
[95]徐梁,张学庸,张纱胤.胃癌特异性免疫脂质体导向治疗的实验研究[J].中华医学杂志,1994,74(2):83.
[96]徐梁,张学庸,吕一辛等.胃癌免疫脂质体导向硼中子俘获治疗的实验研究[J].单克隆抗体通讯,1991,(7)4:1.
[97]Pirollo F,Zon G,Rait A,et al.Tumor-targeting nanoimmunoliposome comolex for short interfering RNA delivery[J].Human Gene Therapy,2006,17(1):117.
[98]Mizuno M,Yoshida J.Repeated exposure to cationic immunoliposomes activates effective gene transfer to human glioma cells[J].Neural Med Hir(Tokyo),1996,36(3):141.
[99]Konigsberg PJ,Godtel R,Kissel T.The development of IL-2 conjugated liposomes for therapeutic purposes[J].Biochim biophys Acta,1998,1370(2):243.
[100]Mamot C,Drummond DC,Noble CO,et al.Epidermal growth factor receptor-targeted immunoliposomes significangly enhance the efficacy of multiple anticancer drugs in vivo[J].Cancer Res,2005,65(24):11631.
[2]陈伟,雷连成,韩文瑜,等利福平脂质体制备工艺的初步研究中国兽药杂志,2002,36(4):24-26
[3]赵荣生,侯新朴,严定霞两性霉素B脂质体的制备及稳定性研究 中国医药工业杂志,2001,32(40:160-162)
[4]王健松,朱家壁 阿奇霉素脂质体的制备及包封率测定 中国药科大学学报,2004,35(6):499-502
[5]穆筱梅,钟振声,陈焕钦果酸脂质体的制备、检测及应用 香料香精化妆品,2002,10(5):25-27
[6]龚金红,刘扬,唐丽华,等盐酸利多卡因脂质体凝胶剂的制备及经皮渗透动力学中国药学杂志,2005,40(11):839-842
[7]五学清,齐宪荣,刘明辉盐酸丁卡因脂质体凝胶剂的制备与释放度的测定中国现代应用药学杂志,2003,20(1):37-40
[8]Rouzi B.Retorolac tromethamine liposome:encapsulation and release studies.J Liposome Res,2005,15(31):175-185.
[9]徐丽君,陆付耳,魏世超等 盐酸小檗碱脂质体的制备方法及质量研究 中国医药药学杂志,2004,24(16):325-326
[10]李维风,牛晓峰,陈海英等PH-梯度-冻融法制备硝苯地平脂质体西安交通大学学报(医学版),2003,24(6):578-580
[11]叶志伟,胡乔红,梁文权粉末床研磨法制备干扰素-脂质体 浙江大学学报(医学版),2002,31(6):433-436
[12]Khuller GK,Kapui M,Sharma S.Liposome technology for drag delivery anainst mycobaterial infections.Curr Pharma Design,2004,10(26):3263-3274.
[13]邓意辉,李焕秋,王绍宁,等主动载药与被动载药制备盐酸左氧氟沙星脂质体 中国抗生素杂志,2001,26(4):40-42
[14]邓意辉,王绍宁,吴琼,等.主动载药法制备盐酸小檗碱脂质体.中国药学杂志,2004,38(1):40-42
[15]杜松,邓英杰,张威.主动载药法制备盐酸去氢骆驼蓬碱脂质体.中草药,2005,36(5):673-676
[16]Allen T M chona,A Large unilia mellar liposomes with low uptake into the reticuliendothelial system[J].FEBS Lett:1987,223:42-46.
[17]赵海霞,郭兴奎,孙德亮,田景振.脂质体制备技术[J].山东中医杂志,2000,19(7):435-437.
[18]顾学裘,马竹卿,辛顺妹等抗癌药新剂型—多相脂质体的研究(Ⅱ)多相脂质体(139,76)混悬液静脉注射液的左究。中划药,1982:13(5):15-20.
[19]Kremer J M H,Vesicles of various diameters by a modified injection method[J].biochemistry,1977,16(17):3932-3935.
[20]阎家麒,童岩,王九一紫杉醇脂质体的制备及其抗瘤的研究[J]药物生物技术,1996,3(3):1-5
[21]李国峰,周日红,曾抗等维生素E脂质体的制备[J]中国应用药学,1997,14(4):18-20
[22]Wang C Y,Yughes K W,Huang L,improved cytoplasmic delivery to plant protoplasts via PH-sensitive liposome[J].Plant ohysiol,1986,82:179-186.
[23]Ropert c,Malvy C,Couvreur P.inhibition if the friend retrovirus by antisense oligonucleotide encapsulatedin liposome[J]mechamism of action,1986,82:179-186.
[24]Szoka F,Olsom F,Preparation of liposome of intermedia size by a combination of reverse phase evaporation and extrusion trough polyamonate membranes[J].Biochm Biophys Acta,1980,601:559-571.
[25]全东琴,苏德林,顾学裘药物载体空白脂质体前体制备及性质的研究[J]沈阳药科大学学报,1999,16(3:160-164.)
[26]GUPTA P K,HUNGC T.Quantitative evaluation of targeted drug delivery systems[J].Int J Pharrn,1989,56(3):217-226.
[27]Crommelin DJA.Liposomes as carries for drus and antiens:approaches to preserve their long term stability[J].Drug Dev Ind Pharm,1994,20(4):547.
[28]Allen TM Long-circuiting(sterically stabilized) liposomes for targeted drug delivery[J]Trends Pharmacol Sci.1994.15(7):215-220
[29]Nagayaso A,Shimooka Y,Kmouchi T,et al Effects of fliodity and vesicle size on antitumor activity and myclosuppressive activity of liposomes loaded with daunorubicin[J].Biol Pharm Bull,1994.17(7):935-939
[30]Nagayasu A.Uchiyama K.Krwada H.The size of liposomes:a factor which affects their targeting efficiency to tumors and therapeutic activity of liposomal antitumor drugs[J]Adv Drug Deliv Rev,1999,40(1):75-87
[31]Yatvin M B,Weinstein J N,Dennie W H,et al.Design of lipomes for enhanced loci release of drugs by hyperthermin[J].Science,1978,202(4374):1290
[32]李建人.高热治疗恶性肿瘤的临床应用[J].国外医学肿瘤学分册,1994,24(4):219.
[33]Chelvi T P,Ralhan R.Hyperthemia potentiates antitumor effect of thermosensitive liposome encapsulated mephalan and radiation in murine melanoma[J].Tumour Biol,1997,18(4):250-260.
[34]Kakinuma K,Tanaka R,Takahushi H,et al.Drug delivery to the brain using thermosensitive liposome and local hyperthermia[J].Int J Hyperthennia,1996,12(1):157-165.
[35]lga K.Ohkouehi K,Ogawa Y,et al.Membrane modification by negatively charged stearyt-polyaxycthylene derivatives for thermosensitive liposomes;reduced liposomal aggregation and avoidance of RES uptake[J].J Drug Target,1994,2(3):259.
[36]Unezaki S,Manuyama K,Takahashi N,et al.Enhanced deliver and antitumor activity of doxorubicin using long-circulating thermosensitive liposomes containing amphipathic polyethylene glycol in combination with local bypenhermia[J].Pharm Res,1994,1(8):1180.
[37]Gaber M H,Hong K,Huang S K,et al.Thermosenstitive sterically stabilized liposomes;formulation and in vitro studies on mechanism of doxorubicin release in bovine serum and human plasma[J].Pharm Res,1995,12(10):1407.
[38]叶伟民,韩焕兴,范列英,等.Bradford比色法简便、快速测定微量蛋白[J].上海医学检验杂志,1996,11(4):207-208
[39]陆斌.免疫分子敏感膜的组装技术研究[D].南京:东南大学,1999.
[40]杨镇.肿瘤免疫学[M].武汉:湖北科学出版社,1998.Nam S M,Kim H S,Ahn W S,et al.Sterically stabilized anti-G(M3),anti-Le(x) immunoliposomes:targeting to B16BL6,HRT-18 cancer cells[J].Oncol Res,1999;11:9-16.
[41]Koning G A,Morselt H W,Velinova M J,et al.Selective transfer of a lipophilic prodrug of 5-fluorodeoxyuridine from immunoliposomes to colon cancer cells[J].Biochim Biophys Acta,2003;1420:153-167.
[1]Okayama R,Noji M,Nakanishi M.Cationic cholesterol with a hydmxyethylamino head group promotes significantly liposome mediated gene transfection.FEBS Lett,1997,408(2):232
[2]Juliano RL,Akhtar S.Liposome as a drug delivery system for antisense oligonucleotides.Antisense Res Dev,1992,2(1):165
[3]Ropert C,Lavignon M,Dubemet C,et al.Oligonucliotides encapsulated in pH sensitive liposomes are efficient toward friend retrovirus.Biochem Biophys Res Commun,1992,183(2):879
[4]Ropert C,Malvy C,Couvreur P.Inhibition of the friend retrovirus by antisense oligonucleotide encapsulated in liposome:mechanism of action.Pharma Res,1993,10(10):1427
[5]Tari AM,Tucker SD,Deisseroth A,et al.Liposome delivery of methyphosphonate antisense oligodeoxynucleotide in chronic myelogenous leukemia.Blood,1994,84(2):601
[6]Lasic DD,Templeton NS.Liposomes in Gene Therapy Adv Drug DelR ev,1996,20(2,3):221
[7]Scan M,Sullivan.Liposome based gene transfer vehicles.Biopharm,1996,50-51:65
[8]Wu XF,Lee KH,Li QT.Stability and pH sensitivity of sulfatide-containing phosphatidylethanolamine small unilamellar vesicles. Biochim Biophy Acta,1996, 1284(1): 13
[9] Jeong MH, Lee YS, Jin JY, et al. pH Sensitive liposomes containing a bipolaramphiphile as a protonatable component. Bull Korean Chem Soc, 1996,17(10): 875
[10] Dzau VJ, Mann MJ, Morishita R, et al. Fusigenic viral liposome for gene therapy in cardiovascular diseases. Proc Natl Acad Sci USA, 1996, 93(21): 11421
[11] Geisert EE, Mar NAD, Owens JL, et al. Transfecting neurons and glia in the rat using pHsensitive immunoliposomes. Neurosci Lett, 1995,184(1): 40
[12] Ma DDF, Wei AQ.Enhanced delivery of synthetic oligonucleotides to human leukemic cells by liposomes and immunoliposomes. Leuk Res, 1996, 20(11/12):925
[13] Slepushkin VA, Simoes S, Dazin P, et al. Sterically stabilized pH sensitive liposomes. Intracellular delivery of aqueous contents and prolonged circulation in vivo. J Biol chem, 1997, 272(4): 2382
[14] Kono K, Igawa T, Takagishi T. Cytoplasmic delivery calcein mediated by liposomes modified with a pH sensitive poly(ethyleneglycol) derivative.Biochim Biophy Acta, 1997,1325(2): 143
[15]Morais P C, Santos J G, Neto K S, et al. Magnetic resonance of magnetic fluid and magnetoliposome preparations. J Magn Magn Mater, 2005, 293: 526
[16] Giri J, Thakurta S G, Bellare J, et al. Preparation and characterization of phospholipid stabilized uniform sized magnetite nanoparticles. J Magn Magn Mater, 2005, 293: 62
[17] Martina M S, Fortin J P, Menager C, et al. Generation Of Superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging. J Am Chem Soc, 2005, 127: 10676
[18] Park J, An K, Hwang Y, et al. Ultra-large-scale syntheses of monodisperse nanocrystals. Nature Mater, 2004, 3: 891
[19] Wang Xun, Zhuang Jing, Peng Qing, et al. A general strategy for nanocrystal synthesis. Nature, 2005, 437: 121
[20] Cuyper M D, PM uller, Lueken H, et al. Synthesis of magnetic Fe3O4 particles covered with a modifiable phospholipids coat. J Phys: Condens Mater, 2003,15: S1425
[21] Kuznetsov A A, Filippo V I, Alyautdin R N, et al. Application of magnetic liposomes for magnetically guided transport of muscle relaxants and anticancer photodynamic drugs. J Magn Magn Mater, 2001, 225: 95
[22]Nawroth T, Rusp M , M ay R P. Magnetic liposomes and entrapping :time-resolved neutron scattering TR-SANS and electron microscopy. Physica B,2004, 350: e635
[23]Jain S, Mishra V, Singh P, et al. ROD-anchored magnetic liposomes for monocytes / neutrophils-mediated brain targeting. Int J Pharmaceutics, 2003,261: 43
[24]Ito K, Shinkai M, Honda H, et al. Medical application of functionalized magnetic nanoparticles. J Biosci Bioeng, 2005, 100(1): 1
[25] Hodenius M, Cuyper M D, Desender I, et al. Biotinylated stealth magnetoliposomes. Chem Phys Lipids, 2002,120: 75
[26]Dominno J C, Mercadal M, Petriz J, et al. Preparation of PPG-grafted immunomannetoliposomes entrapping citrate stabilized mannetite particles and their application in CD34+cell sorting. J Microencapsulation, 2001,18(1):41
[27] Dumitrascu G, Kumbhar A, Zhou W L, et al. The use of derivatized magnetoliposomes for extraction of antibodies from aqueous solutions. IEEE Trans Magnetics, 2001, 37(4): 2932.
[28] Zhang J Q, Zhang Z R, Yang H, et al. Lyophilized paclitaxel magnetoliposomes as a potential drug delivery system for breast carcinoma via parenteral administration: in vitro and in vivo studied. Pharmaceutical Res, 2005,22(4):573.
[29] Kullberg M, Mann K, Owens J L. Improved drug delivery to cancer cells: a method using magnetoliposomes that target epidermal growth factor receptors.Medical Hypotheses, 2005, 64:468.
[30] Hamaguchi S, Tohnai I, Ito A, et al. Selective hyperthermia using magnetoliposomes to target cervical lymph node metastasis in a rabbit tongue tumor model. Cancer Sci, 2003,94(9):834.
[31] Kawai N, Ito A, Nakahara Y, et al. Anticancer effect of hyperthermia on prostate cancer mediated by magnetite cationic liposomes and immune response induction in transplanted syngeneic rats. The Prostate, 2005, 64: 373.
[32] Ito A, Shinkai M, Honda H, et al. Heat shock protein 70 expression induces antitumor immunity during intracellular hyperthermia using magnetite nanoparticles. Cancer Immunol Immunother, 2003, 52:80.
[33] Matsuoka F, Shinkai M, Honda H, et al. Hyperthermia using magnetite cationic liposomes for hamster osteosarcoma. Biomagnetic Res Techn, 2004,2:3.
[34] Yatvin M B, Weinstein J N, Dennie W H, et al. Design of lipomes for enhanced locl release of drugs by hyperthermin [J]. Science, 1978, 202(4374): 1290.
[35]李建人.高热治疗恶性肿瘤的的临床应用[J].国外医学肿瘤学分册, 1994,24(4):219.
[36] Chelvi T P, Ralhan R. Hyperthemia potentiates antitumor effect of thermo-sensitive liposome encapsulated mephalan and radiation in murine melanoma [J].Tumour Biol, 1997, 18(4): 250-260.
[37] Kakinuma K, Tanaka R, Takahushi H, et al. Drug delivery to the brain using thermosensitive liposome and local hyperthermia [J]. Int J Hyperthermia, 1996,12(1): 157-165.
[38] lga K. Ohkouehi K, Ogawa Y, et al. Membrane modification by negatively charged stearyt-polyaxycthylene derivatives for thermosensitive liposomes;reduced liposomal aggregation and avoidance of RES uptake [J]. J Drug Target,1994,2(3):259.
[39] Unezaki S, Manuyama K, Takahashi N, et al. Enhanced deliver and antitumor activity of doxorubicin using long-circulating thermosensitive liposomes containing amphipathic polyethylene glycol in combination with local bypenhermia [J]. Pharm Res, 1994,1(8): 1180.
[40] Gaber M H, Hong K, Huang S K, et al. Thermosenstitive sterically stabilized liposomes; formulation and in vitro studies on mechanism of doxorubicin release in bovine serum and human p lasma [J]. Pharm Res, 1995, 12(10):1407.
[41] Vitoonchatapan E, Sato H, Vero M, et al. Megnetie targeting of thermosensitive magnetoliposomes to mouse livers in an in situ on line perfusion system [J]. Life Sci, 1996, 58 (24): 2251.
[42] Sullivan S M. Huang L. Preparation and characterization of heat sensitive immunoliposome [J]. Biochim Biophys Acta, 1985, 816(1):116.
[43] Schild H G, Tirrell D A. Microscalorimetric detection of lever critical solution temperature in quenous polymer solution [J]. J Phys Chem, 1990, 94 (1):4352-4356.
[44] Kim J C, BaeSoo K, Kim J D. Temperature-sensitivity of liposomal lipid bilayers mixed with poly(N-isopropylacry lamide)-co-acrylic acid [J]. J Biochem, 1997, 121(1):15-19.
[45]Hayashi H,Kono K,Takagishi T.Temperature-controlled release property of phospholipids vesicles beating a thermosensitive polymer[J].Biochem Biophys Acta,1996,1280(1):127-134.
[46]赵峰等,天然大豆磷脂制备热敏脂质体的方法及质量评价[J].中国天然药物,2005,3(4):7.
[47]邢同京.免疫脂质体研究进展[J].国外医学预防、诊断、治疗用生物制品分册,2002,(21):214-217.
[48]陆斌.免疫分子敏感膜的组装技术研究[D].南京:东南大学,1999.
[49]徐梁,张学庸,莫简.胃癌特异性免疫脂质体的制备及其体内外抗肿瘤作用[J].第四军医大学学报,2002,(12):68-72.
[50]Truneh A,Machy P,Horan P K,et al.Antibody bearing liposomesas multicolor immunofluorescence markers for flowcytometry and imaging[J].JImmunol-Methods,1987,100:59-65.
[51]Sriwongsitanont S,Ueno M.Physicochemical properties of PEG-grafted Liposomes.Chem Pharm Bull,2002,50:1238-1244.
[52]Allen TM,Brandeis E,Hansen CB,et al.A new strategy for attach mentofantibodies to sterically stabilized liposomes resulting in efficient targeting to cancer cells.Biochim Biophys Acta,1995,1237:99-108.
[53]Hawyler J,Yang J,Pardridge WM.Receptor mediated delivery of dannomycin using immunoliposomes:pharmacokineties and tissue distribution in the rat.J Pharmacol Exp Ther,1997,282:1541-1546.
[54]Harding JA,Engbers CM,Newman MS,et al.Immunogenicity and pharmacokinetic attributes of poly(ethyleneglycol)-grafted immunolipsomes.Biochim Biophys Acta,1997,1327:181-192.
[55]Dams ET,Laverman P,Oyen WJ,et al.Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes.J Pharmacol ExpTher,2000,292:1071-1079.
[56]Bendas G,Rothe U,Scherphof GL.et al.The influence of repeated injections on pharmacokinetics and biodistrobution of different types of sterically stabilized immunoliposomes.Biochim Biophys Acta,2003,1069:63-70.
[57]Laverman P,Carstens MG,Boerman OC,et al.Factors affecting the accelerated blood clearance of polyethylene glycol liposomes upon repeated injection.J pharmacol ExpTher,2001,298:607-612.
[58] Goins B, Phillips WT, Klippers R. Repeat injection studies of technetium 99m-labeled PEG-liposomes in some animal. J Liposome Res, 1998, 8: 265-281.
[59] Oussoren C, Storm G. Effect of repeated intravenous administration on the circulation kinetics of poly(ethyleneglycol)-liposomes in cat. J Liposomes Res,1999,9:349-355.
[60] Utkhede DR, Tilcock CP. Effect of lipid dose on the biodistrbution and blood pool clearance kinetics of PEG-modified technetium-labeled lipid vesicles. J Liposomes Res, 1998, 8: 381-390.
[61] Laverman P, Brouwers AH, Dams ET, et al. Preclinical and clinical evidence for disappearance of long-circulating characteristic of polyethyleneglycol liposomes at low lipid dose. J Pharmacol Exp Ther, 2000, 293:996-1001.
[62] YuanF, Dellian M, Fukumura D. Vascular permeability in a human tumor xenograft: molecular size dependence and cut off size. Cancer Res, 1995, 55:3752-3756.
[63] Hobbs SK, Monsky WL, Yuan F. Regulation of transport pathways in tumor vessels: role of tumor type and micro environment. Proc Natl Acad Sci USA,1998,95:4607-4612.
[64] Brown JM, Giaccico AJ. The unique physiology of solid tumors: Opportunities (and problems) for cancer therapy. Cancer Res, 1998, 58: 1408-1416.
[65] Jain RK. Delivery of molecular and cellular medicine to solid tumors. J Control Release, 1998, 53: 49-67.
[66] Allen TM, Ahmad I, Lopes de Menezes DE, et al. Immunoliposomes mediated targeting of anti-cancer drugs in vivo. Biochim SocTrans, 1995, 23: 1073-1079.
[67] Park JW, Hong K, Kirpotin DB, et al. Anti-HER2 immunoliposomes for targeted therapy of human tumors. Cancer Lett, 1997, 118: 153-160.
[68] Lopes de Menezes DE, Pilarski LM, AllenTM. In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-celllymphorma. Cancer Res, 1998,58: 3320-3330.
[69] Koning GA, Morselt HW, Velinova MJ,et al. Selective transfer of a lipophilic prodrug of 5-fluo-rodeoxyuridine from immunoliposomes to colon cancer cells.Biochim Biophys Acta, 1999,1420: 153-167.
[70] Sarti P, Ginohhi P, Agostino ID, et al. HL-60 cells induced by transferic-receptor endocytosis. Biotemich Apl Biochem, 1996,24: 269-276.
[71] Park JW, Hong K, Carter P, et al. Development of anti-p185HER2 immunoliposomes for cancer therapy.Proc Natl Acad Sci USA,1995,92:1327-1331.
[72]Goren D,Horowifz AT,Zalipsky S,et al.Targeting of stealth liposomes to erbB-2(Her/2) receptor in vitro and in vivo studies.Brit J Cancer,1996,74:1749-1756.
[73]LiX,Stuckert P,BoschI,et al.Single-chain antibody-mediated gene delivery into ErbB2-position human breast cancer cells.Cancer Gene Ther,2001,8:555-565.
[74]Park JW,Kirpotin DB,HongK,et al.Tumor targeting using anti-her2immunoliposomes.J Control Release,2001,74:95-113.
[75]Park JW,Hong K,Kirpotin DB,et al.Anti-HER2 immunoliposomes:enhanced efficacy attributable to targeted delivery.Clin Cancer Res,2002,8:1172-1181.
[76]Sugano M,Egilmez NK,Yokota S J,et al.Antibody targeting of doxorubicin-loaded liposomes suppresses the growth and metastatic spread of established human lung tumor xenografts in severe combined immunodeficient mice.Cancer Res.2000,60:6942-6949.
[77]杨镇.肿瘤免疫学[M].武汉:湖北科学出版社,1998.
[78]Nam S M,Kim H S,Ahn W S,et al.Sterically stabilized anti-G(M3),anti-Le(x)immunoliposomes:targeting to B16BL6,HRT-18 cancer cells[J].Oncol Res,1999;11:9-16.
[79]Koning G A,Morselt H W,Velinova M J,et al.Selective transfer of a lipophilic prodrug of 5-fluorodeoxyufidine from immunoliposomes to colon cancer cells[J].Biochim Biophys Acta,2003;1420:153-167.
[80]王华.旋毛虫幼虫单克隆抗体制备和鉴定[J].北京医科大学学报,1988,20(4):285.
[81]徐梁,张学庸,莫简,等.胃癌特异性阿霉素免疫脂质体的制备及其特性[J].中华消化杂志,1999,6:325-328
[82]全东琴,苏德森,顾学裘.由空白脂质体制备抗癌药物脂质体[J].沈阳药科大学学报,1999,16(4):239.
[83]朱盛山 主编.药物新剂型[M].第1版.北京:化学工业出版社,2003:460.
[84]侯新朴,张宇锋,谢蜀生等.第3代载药免疫脂质体及体内外寻靶研究[J].药学学报,2001,36(7):539.
[85]Anne MR,Jonathan EG,Malcolm NL.The specificity and affinity of immunoliposome targeting to oral bacterial[J].Biochim Biophys Acta,1998,1369(2):278.
[86]牛荣丽,薛弘燮,李志良.阿苯达唑免疫脂质体的制备[J].新疆医科大学学报,2001,24(1):60.
[87]王述亘,安国顺,程道新.免疫脂质体作为阿苯达唑载体治疗小鼠泡球蚴病实验研究.[J].寄生虫与医学昆虫学报,1997,4(4):211.
[88]Chuyder A,Huwyler J.Drug transport to brain with targeted liposomes[J].Neuro Rx,2005,2(1):99.
[89]chekhonin VP,Zhirkov IA,Gurina O1.Production and characteristics of PEGylated immunoliposome transport vectors specific for neural tissue astrocytes[J].Biomed Khim,2005,51(3):276.
[90]Huwyler J,Wu D,Pardridge WM.Brain drug delivery of small molecules using immunoliposomes[J].Proc Natl Acac Sci USA,1996,93(24):14164
[91]Shi N,Pardidge WM.Non-invasive gene targeting to the brain[J].Proc Natl Acad Sci USA,2000,97(13):7567.
[92]方瑾,王芸庆,宋今丹紫杉醇免疫脂质体的制备及其对大肠癌的杀伤作用[J].中华微生物学和免疫学杂志,1997,17(1):59.
[93]方瑾,王芸庆,宋今丹.大肠癌免疫脂质体导向紫杉醇的实验研究[J].中国免疫学杂志,1998,14(3):198.
[94]李文锦,钱和年,吕文英,等.免疫脂质体对卵巢癌细胞生长抑制实验的研究[J].北京医科大学学报,1994,25(3):184.
[95]徐梁,张学庸,张纱胤.胃癌特异性免疫脂质体导向治疗的实验研究[J].中华医学杂志,1994,74(2):83.
[96]徐梁,张学庸,吕一辛等.胃癌免疫脂质体导向硼中子俘获治疗的实验研究[J].单克隆抗体通讯,1991,(7)4:1.
[97]Pirollo F,Zon G,Rait A,et al.Tumor-targeting nanoimmunoliposome comolex for short interfering RNA delivery[J].Human Gene Therapy,2006,17(1):117.
[98]Mizuno M,Yoshida J.Repeated exposure to cationic immunoliposomes activates effective gene transfer to human glioma cells[J].Neural Med Hir(Tokyo),1996,36(3):141.
[99]Konigsberg PJ,Godtel R,Kissel T.The development of IL-2 conjugated liposomes for therapeutic purposes[J].Biochim biophys Acta,1998,1370(2):243.
[100]Mamot C,Drummond DC,Noble CO,et al.Epidermal growth factor receptor-targeted immunoliposomes significangly enhance the efficacy of multiple anticancer drugs in vivo[J].Cancer Res,2005,65(24):11631.