叶酸受体介导多西他赛肿瘤靶向长循环脂质体的研究
|
摘要
叶酸受体介导的长循环脂质体是近年来主动靶向制剂研究的重点之一。本文选用多西他赛(DTX)为模型药物,制备了多西他赛长循环脂质体和多西他赛长循环固体脂质纳米粒,并进行了处方、工艺考察,使用效应面法优化了两种长循环纳米制剂的最优处方。在此基础上,制备了叶酸受体介导的多西他赛长循环脂质体,研究了叶酸受体介导的多西他赛长循环脂质体在体内外的靶向性,初步探讨其靶向机理,使用荷瘤裸鼠考察了叶酸受体介导的多西他赛长循环脂质体抑制肿瘤的效果。
以多西他赛为模型药物制备了多西他赛长循环脂质体,实验以包封率为指标考察了处方及工艺对制剂包封率的影响,并以效应面法确定优化处方。最终处方为SPC:DTX (20:1)、SPC:Chol(3:1). SPC浓度3%、PEG2000-Chol浓度5%。多西他赛长循环脂质体的包封率为90.42±3.25%,粒径为117.6±5.34 nm；透射电镜下观察脂质体为单室脂质体,呈圆形或类圆形,粒径结果与LS 230激光粒度仪测定结果相符。24 h释放度为62.3±3.12%。在大鼠血浆中,脂质体释放加快。室温放置一个月,制剂稳定性良好。为长期保存多西他赛长循环脂质体,制备了多西他赛长循环冻干脂质体,制剂稳定性良好。
以多西他赛为模型药物制备了多西他赛长循环固体脂质纳米粒,实验以包封率、粒径为指标考察了处方及工艺对制剂包封率、粒径的影响,并以效应面法确定优化处方。最终处方为脂质浓度为5%、乳化剂用量为5%(磷脂浓度为2.5%,F68浓度为2.5%)、脂质与药物比为20：1、DOPE-PEG浓度为7%。多西他赛长循环固体脂质纳米粒的包封率为93.1士4.3%,粒径为136.4±11.2 nm；透射电镜下观察纳米粒为类球形实体粒子,粒度分布均匀。在含有0.5%Tween-80的水溶液中,释放前2h,纳米粒有大约30%的药物发生突释,释放24h时纳米粒均未释放完全,表明纳米粒具有缓释能力。
合成新型靶向辅料胆固醇-PEG-叶酸(Chol-PEG-Fol),使用IR、NMR等初步鉴定为目的产物。在多西他赛长循环脂质体处方研究基础上,使用Chol-PEG-Fol制备叶酸受体介导的多西他赛长循环脂质体(Fol-PEG-DTXL)。
使用荧光标记的Fol-PEG-DTXL定量考察了Fol-PEG-DTXL在MCF-7细胞的结合量。流式细胞仪检测、荧光显微镜观察,推断Fol-PEG-DTXL是通过叶酸介导的细胞内化被细胞内吞。体外细胞毒实验证明、Fol-PEG-DTXL比PEG-DTXL更有效地抑制MCF-7细胞的生长(P<0.01),而Fol-PEG-DTXL与PEG-DTXL对Hela细胞的抑制无显著性差别(P>0.05),加入游离叶酸可抑制Fol-PEG-DTXL对MCF-7细胞的细胞毒作用,而对Hela细胞无效。BALB/c裸鼠体内抑瘤实验发现,Fol-PEG-DTXL可有效抑制体内肿瘤生长,抑瘤率为67.6%,较其它制剂组有显著性差别(P<0.01)。
使用wastar大鼠考察了Fol-PEG-DTXL的体内药动学参数。DTX溶液的t1／2为1.157h,DTXL的t1／2为3.08 h,PEG-DTXL的t1／2为7.795 h,为DTX溶液的2.66倍,DTXL的6.74倍。Fol-PEG-DTXL的MRT0-t、MRT0-∞分别为注射剂组的5.5和5.26倍；DTXL的3.32和3.10倍。表明Fol-PEG-DTXL可以显著延长DTX的体内循环时间。此结果提示Fol-PEG-DTXL可有效降低多西他赛的毒副作用,达到安全用药的目的。昆明种小鼠体内组织分布研究发现,多西他赛溶液剂在小鼠体内分布较为迅速、广泛,具有一定透过血脑屏障的能力,且可能对心脏产生急性或慢性毒性。叶酸介导多西他赛长循环脂质体相比多西他赛溶液和多西他赛普通脂质体具有较为明显的增加体内循环时间的作用,同时,能减少药物向心和脑中的分布,降低多西他赛对心、脑的毒性作用。
Recently, the long-circulating liposomes mediated by folate receptor have attracted considerable attention as drug targeting delivery. In present study, Docetaxel (DTX) was used as a model drug and used to prepare DTX loaded long-circulating liposomes and DTX loaded long-circulating solid lipid nanoparticles. The effect of some factors on the formulations and preparation of these two long-circulating nanocarries was investigated. Furthermore, the response surface methodology was used to optimize these two long-circulating nanocarriers. The long-circulating liposomes mediated by folate receptor were also prepared. The targetability and growth inhibition of immunoliposomes on MCF-7 cells in vitro and Balb/c nude mice in vivo was also studied.
The long-circulating liposomes were prepared with DTX and the effect of some factors on the encapsulation efficiency was investigated. Then the formulation was optimized by the response surface methodology. Finally, the long-circulating liposomes were prepared by SPC: DTX (20:10、SPC:Chol(3:1),3% of SPC in water and 5% molar ratio of SPC with the encapsulation efficiency of 90.42±3.25% and the particle distribution of 117.6±5.34 nm. The liposomes were single unilamellar vesicles and spherical under TEM. The cumulative release within 24 h was 62.3±3.12%, and the release rate of liposomes raised in rat plasma. To store for long time, the long-circulating liposomes were freeze-drying.
The long-circulating solid lipid nanoparticles were prepared with DTX and the effect of some factors on the encapsulation efficiency and particle size was investigated. Then the formulation was optimized by the response surface methodology. Finally, the long-circulating SLN were prepared by 5% in water,、5% of emulsifier in water (SPC:F68 1:1)、lipid/DTX (20:1)、7% of DOPE-PEG with the encapsulation efficiency of 93.1±4.3% and the particle distribution of 136.4±11.2 nm。The SLNs were spherical under TEM. In water with Tween-80 (0.5%),30% of DTX was released within the first 2h, however, DTX didn't release completely at the 24th h.
Chol-PEG-Folic acid (Chol-PEG-Fol) was synthesized and analyzed with IR, NMR. Using Chol-PEG-Fol, the long-circulating liposome mediated by folate receptor (Fol-PEG-DTXL) was prepared and investigated.
Results of flow cytometer and fluorescence microscopy, suggested the liposome internalized in cells mediated by folic acid. Fool-PEG-DTXL was more catatonic on MCF-7cells than PEG-DTXL (P<0.01), when cytotoxicties were compared for Hela cells, no significant differences were observed between Fol-PEG-DTXL and PEG-DTXL (P>0.05), suggesting that Fol-PEG-DTXL showed relative selective cytotoxicity on MCF-7 cells. The additional folic acid reduced the cytotoxicity on MCF-7 cells, but no effect on Hela cells. Using Balb/c nude mice bearing MCF-7 cells, we compared the antitumor efficacy of liposomal DTX and DTX. The treatment with DTX, liposomal DTX inhibited primary tumor growth of MCF-7cells compared with the control group. Furthermore, five injections of Fol-PEG-DTXL resulted in substantial tumor regressions, and tumor regressions in the Fol-PEG-DTXL group were significantly greater than in the non-targeted groups (P<0.05) and far superior to the control PBS treatment (P<0.01). The antitumor efficacy of Fol-PEG-DTXL was 67.6%.
The pharmacokinetic parameters of Fol-PEG-DTXL were studied in Wister rat. The t1/2 of DTX, DTXL and Fol-PEG-DTXL were 1.157 h,3.08 h, and 7.795 h, respectively. The t1/2 of Fol-PEG-DTXL was 6.74-fold to DTX, and 2.66-fold to DTXL. MRT0-t and MRT0-∞of Fol-PEG-DTXL were 5.5-fold and 5.26-fold to DTX,3.32-fold and 3.10-fold to DTXL These results suggested Fol-PEG-DTXL reduced the toxicity of DTX. The results of biodistribution in mouse suggested docetaxel solution distributed rapidly and extensively, could somehow penetrate the blood brain barrier, and cause acute and chronic cardiac toxicity. Compared to DTX and DTXL, Fol-PEG-DTXL enhanced the time in blood. DTX distribution in heart、brain and kidney were decreased, which could depress DTX side effects on these organs.
以多西他赛为模型药物制备了多西他赛长循环脂质体,实验以包封率为指标考察了处方及工艺对制剂包封率的影响,并以效应面法确定优化处方。最终处方为SPC:DTX (20:1)、SPC:Chol(3:1). SPC浓度3%、PEG2000-Chol浓度5%。多西他赛长循环脂质体的包封率为90.42±3.25%,粒径为117.6±5.34 nm；透射电镜下观察脂质体为单室脂质体,呈圆形或类圆形,粒径结果与LS 230激光粒度仪测定结果相符。24 h释放度为62.3±3.12%。在大鼠血浆中,脂质体释放加快。室温放置一个月,制剂稳定性良好。为长期保存多西他赛长循环脂质体,制备了多西他赛长循环冻干脂质体,制剂稳定性良好。
以多西他赛为模型药物制备了多西他赛长循环固体脂质纳米粒,实验以包封率、粒径为指标考察了处方及工艺对制剂包封率、粒径的影响,并以效应面法确定优化处方。最终处方为脂质浓度为5%、乳化剂用量为5%(磷脂浓度为2.5%,F68浓度为2.5%)、脂质与药物比为20：1、DOPE-PEG浓度为7%。多西他赛长循环固体脂质纳米粒的包封率为93.1士4.3%,粒径为136.4±11.2 nm；透射电镜下观察纳米粒为类球形实体粒子,粒度分布均匀。在含有0.5%Tween-80的水溶液中,释放前2h,纳米粒有大约30%的药物发生突释,释放24h时纳米粒均未释放完全,表明纳米粒具有缓释能力。
合成新型靶向辅料胆固醇-PEG-叶酸(Chol-PEG-Fol),使用IR、NMR等初步鉴定为目的产物。在多西他赛长循环脂质体处方研究基础上,使用Chol-PEG-Fol制备叶酸受体介导的多西他赛长循环脂质体(Fol-PEG-DTXL)。
使用荧光标记的Fol-PEG-DTXL定量考察了Fol-PEG-DTXL在MCF-7细胞的结合量。流式细胞仪检测、荧光显微镜观察,推断Fol-PEG-DTXL是通过叶酸介导的细胞内化被细胞内吞。体外细胞毒实验证明、Fol-PEG-DTXL比PEG-DTXL更有效地抑制MCF-7细胞的生长(P<0.01),而Fol-PEG-DTXL与PEG-DTXL对Hela细胞的抑制无显著性差别(P>0.05),加入游离叶酸可抑制Fol-PEG-DTXL对MCF-7细胞的细胞毒作用,而对Hela细胞无效。BALB/c裸鼠体内抑瘤实验发现,Fol-PEG-DTXL可有效抑制体内肿瘤生长,抑瘤率为67.6%,较其它制剂组有显著性差别(P<0.01)。
使用wastar大鼠考察了Fol-PEG-DTXL的体内药动学参数。DTX溶液的t1／2为1.157h,DTXL的t1／2为3.08 h,PEG-DTXL的t1／2为7.795 h,为DTX溶液的2.66倍,DTXL的6.74倍。Fol-PEG-DTXL的MRT0-t、MRT0-∞分别为注射剂组的5.5和5.26倍；DTXL的3.32和3.10倍。表明Fol-PEG-DTXL可以显著延长DTX的体内循环时间。此结果提示Fol-PEG-DTXL可有效降低多西他赛的毒副作用,达到安全用药的目的。昆明种小鼠体内组织分布研究发现,多西他赛溶液剂在小鼠体内分布较为迅速、广泛,具有一定透过血脑屏障的能力,且可能对心脏产生急性或慢性毒性。叶酸介导多西他赛长循环脂质体相比多西他赛溶液和多西他赛普通脂质体具有较为明显的增加体内循环时间的作用,同时,能减少药物向心和脑中的分布,降低多西他赛对心、脑的毒性作用。
Recently, the long-circulating liposomes mediated by folate receptor have attracted considerable attention as drug targeting delivery. In present study, Docetaxel (DTX) was used as a model drug and used to prepare DTX loaded long-circulating liposomes and DTX loaded long-circulating solid lipid nanoparticles. The effect of some factors on the formulations and preparation of these two long-circulating nanocarries was investigated. Furthermore, the response surface methodology was used to optimize these two long-circulating nanocarriers. The long-circulating liposomes mediated by folate receptor were also prepared. The targetability and growth inhibition of immunoliposomes on MCF-7 cells in vitro and Balb/c nude mice in vivo was also studied.
The long-circulating liposomes were prepared with DTX and the effect of some factors on the encapsulation efficiency was investigated. Then the formulation was optimized by the response surface methodology. Finally, the long-circulating liposomes were prepared by SPC: DTX (20:10、SPC:Chol(3:1),3% of SPC in water and 5% molar ratio of SPC with the encapsulation efficiency of 90.42±3.25% and the particle distribution of 117.6±5.34 nm. The liposomes were single unilamellar vesicles and spherical under TEM. The cumulative release within 24 h was 62.3±3.12%, and the release rate of liposomes raised in rat plasma. To store for long time, the long-circulating liposomes were freeze-drying.
The long-circulating solid lipid nanoparticles were prepared with DTX and the effect of some factors on the encapsulation efficiency and particle size was investigated. Then the formulation was optimized by the response surface methodology. Finally, the long-circulating SLN were prepared by 5% in water,、5% of emulsifier in water (SPC:F68 1:1)、lipid/DTX (20:1)、7% of DOPE-PEG with the encapsulation efficiency of 93.1±4.3% and the particle distribution of 136.4±11.2 nm。The SLNs were spherical under TEM. In water with Tween-80 (0.5%),30% of DTX was released within the first 2h, however, DTX didn't release completely at the 24th h.
Chol-PEG-Folic acid (Chol-PEG-Fol) was synthesized and analyzed with IR, NMR. Using Chol-PEG-Fol, the long-circulating liposome mediated by folate receptor (Fol-PEG-DTXL) was prepared and investigated.
Results of flow cytometer and fluorescence microscopy, suggested the liposome internalized in cells mediated by folic acid. Fool-PEG-DTXL was more catatonic on MCF-7cells than PEG-DTXL (P<0.01), when cytotoxicties were compared for Hela cells, no significant differences were observed between Fol-PEG-DTXL and PEG-DTXL (P>0.05), suggesting that Fol-PEG-DTXL showed relative selective cytotoxicity on MCF-7 cells. The additional folic acid reduced the cytotoxicity on MCF-7 cells, but no effect on Hela cells. Using Balb/c nude mice bearing MCF-7 cells, we compared the antitumor efficacy of liposomal DTX and DTX. The treatment with DTX, liposomal DTX inhibited primary tumor growth of MCF-7cells compared with the control group. Furthermore, five injections of Fol-PEG-DTXL resulted in substantial tumor regressions, and tumor regressions in the Fol-PEG-DTXL group were significantly greater than in the non-targeted groups (P<0.05) and far superior to the control PBS treatment (P<0.01). The antitumor efficacy of Fol-PEG-DTXL was 67.6%.
The pharmacokinetic parameters of Fol-PEG-DTXL were studied in Wister rat. The t1/2 of DTX, DTXL and Fol-PEG-DTXL were 1.157 h,3.08 h, and 7.795 h, respectively. The t1/2 of Fol-PEG-DTXL was 6.74-fold to DTX, and 2.66-fold to DTXL. MRT0-t and MRT0-∞of Fol-PEG-DTXL were 5.5-fold and 5.26-fold to DTX,3.32-fold and 3.10-fold to DTXL These results suggested Fol-PEG-DTXL reduced the toxicity of DTX. The results of biodistribution in mouse suggested docetaxel solution distributed rapidly and extensively, could somehow penetrate the blood brain barrier, and cause acute and chronic cardiac toxicity. Compared to DTX and DTXL, Fol-PEG-DTXL enhanced the time in blood. DTX distribution in heart、brain and kidney were decreased, which could depress DTX side effects on these organs.
引文
[1]Robert W. Atcherad, Michael G. Stabinc, et al. Somatostatin-receptor-targeted a-emitting 213Bi is therapeuticallymore effective than β-emitting177Lu in human pancreatic adenocarcinoma cells. Nuclear Medicine and Biology 34:185-193
[2]De Jong M, Breeman WA, Bernard BF, Bakker WH, Schaar M, VanGameren A, et al. [177Lu-DOTA0,Tyr3] octreotate for somatostatinreceptor-targeted radionuclide therapy. Int J Cancer 92:628-633
[3]马寄晓,叶大铸.奥曲肽及其类似物用于肿瘤治疗的进展,国外医学.放射医学核医学分册,29(2)：79-83
[4]David Raben, Murray Stackhouse, Donald J. Buchsbaum, Galeena Mikheeva, M. B. Khazaeli, et al. 2207 Genetic induction of the gastrin releasing peptide receptor on tumor cells for radiolabeled peptide binding, International Journal of Radiation Oncology*Biology*Physics,36 (1):378-389.
[5]Stackhouse MA. Buchsbaum DJ. Kancharla SR. Specific membrane receptor gene expression targeted with radiolabeled peptide employing the erbB-2 and DF3 promoter elements in adenoviral vectors. Cancer Gene Therapy,6 (3):209-19
[6]Buck E. Rogers, Donald J. Buchsbaum, Richard L. Kirkman,et al. In Vivo Localization of [111In]-DTPA-D-Phel-Octreotide to HumanOvarian Tumor Xenografts Induced to Express the SomatostatinReceptor Subtype 2 Using an Adenoviral Vector1. Clinical Cancer Research,5:383-393
[7]H. Shimura, K. Haraguchi, A. Miyazaki, T. Endo, T. Onaya, Iodide uptake and experimental 131I-therapy in transplanted undifferentiatedthyroid cancer cells expressing the Na/I-symporter gene,Endocrinology 138:4493-4496
[8]Zhang, L. Sharma, S. Hershman, J. M. Iodide sensitizes genetically modified non-small cell lung cancer cells to ionizing radiation. Cancer Gene Therapy; Jan2006,13 (1), p74-81
[9]Achim Wenzel, Geeta Upadhyay, Thomas L. Schmitt and Ulrich Loos, Iodination of proteins in TPO transfected thyroid cancer cells is independent of NIS. Molecular & Cellular Endocrinology,213 (1):99-108
[10]Lasic DD, Papahadjopoulos D, Liposomes revisited. Science,1995,267:1275-1276
[11]Papahadjopoulos D, Allen TM, Gabizon A, et al. Sterically stabilized liposomes:improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci USA,1991,88:11460-11464
[12]Klibanov AL, Maruyama K, Torchilin VP, et al. Amphipathic polyethyleneglycols effectively prolong the circulation times of liposomes. FEBS Lett,1990,268:235-237
[13]Harrington KJ, Lewanski CR, Stewart JSW, Liposomes as vehicles for targeted therapy of cancer. Part 1:Preclinical development. Clin. Oncol (R Coll Radiol),2000,12:2-15
[14]A. T. M. Vaughan, A. R. Bradwell, P. W. Dykes and P. Anderson, Illusions of tumour killing using radiolabelled antibodies, The Lancet,327, (8496):1492-1493
[15]Ko AH, Tempero MA. Treatment of metastatic pancreatic cancer, JNatl Compr Cancer Netw, 2005,3:627-36
[16]Jo Whelan, Beyond PEGylation, DDT,10 (5):301.
[17]Dadachova E. Bouzahzah B. Zuckier LS. Pestell RG. Rhenium-188 as an alternative to Iodine-131 for treatment of breast tumors expressing the sodium/iodide symporter (NIS), Nuclear Medicine & Biology,29 (1):13-18.
[18]Boyd M. Cunningham SH. Brown MM. Mairs RJ. Wheldon TE. Noradrenalin transporter gene transfer for radiation cell kill by 1311 meta-iodobenzylguanidine, Gene Therapy.6 (6):1147-52
[19]Juweid ME, Hajjar G, Swayne LC, et al. Phase 1/Ⅱ trial of 131I-MN-14F(ab)2:anti carcinoembryonic antigen monoclonal antibody in the treatment of patients with metastatic medullary thyroid carcinoma.Cancer,85 (6):1828-1840
[20]Sengelov L, von der Maase H. Radiotherapy in bladder cancer. Radiother Oncol,52 (1):1-14
[21]Lesley Wilsona, Marie Boyd, et al. Application of Targeted Radiotherapy/GeneTherapy to Bladder Cancer Cell Lines, European Urology 47:250-256
[22]Shuji Tanada, Hajime Murata, Yasuhito Sasaki, et al. Labeling of Phosphorothioate Antisense Oligonucleotideswith Yttrium-90, Nuclear Medicine & Biology,26:239-243
[23]Guvakova M. A., Yakubov L. A., Vlodavsky I., Tonkinson J. L. andStein C. A. Phosphorothioate oligodeoxynucleotides bind to basic fibroblast growth factor, inhibit its binding to cell surfacereceptors, and remove it from low affinity binding sites on extracellular matrix, Biol. Chem. 270:2620-2627
[24]Ho P. T. C. and Parkinson D. R. Antisense oligonucleotides astherapeutics for malignant diseases. Semin. Oncol,24:187-202
[25]徐玉清,文雪梅。多西他赛磁微球的制备。哈尔滨医科大学学报,2005,39(6)：537-539
[26]lmmordino ML, Bmsa P, Arpicco S, et al. Preparation characterization cytotoxicity and pharmacokinetics of liposomes containing docetaxel. J Controlled Release,2003,91(4):417-429
[27]杜振新,卢秀莲,李大涛等。一种含有多西他赛的脂肪乳剂及其制备方法：中国,200510084055,6[P]。2005-12-21
[28]张先林。抗肿瘤药多西紫杉醇制剂的应用研究近况。药学进展,2006,30：516-520
[1]Papahadjopoulos D, Allen T, Gabizon A, et al, Sterically stabilized liposomes:improvements in pharmacokinetics and anti-tumor efficacy. Proc. Natl. Acad. Sci. USA,1991,88:11460-11464
[2]Anees A, Karnachi, Mansoor A.Khan. Box-behnken design for the optimization of formulation variables of indomethacin coprecipitates with polymer mixtures[J]. International Journal of Pharmaceutics.1996,131:9-17.
[3]Mohammad TH, Mahmoud S, Soliman, et al. Optimization and characterization of controlled release multi-particulate beads coated with starch acetate[J]. International Journal of Pharmaceutics.2005, 294:89-101.
[4]吴伟,崔光华.星点设计-效应面优化法及其在药学中的应用[J].国外医学药学分册.2000,27(5)：292-297.
[5]赵荣生,候新朴,严宝霞.脂质体载体材料卵磷脂的制备及质量标准研究[J].中国现代应用药学杂志.2001,1(18)：39-41.
[6]Gabizon, Papahadjopoulos D. The role of surface charge and hydrophilic groups on liposome clearance in vivo[J]. Biochim Biophys Acta.1992,1103(1):94-100.
[7]胡兰荣,董志伟.掺入胆固醇和阴离子磷脂对阿霉素免疫脂质体性能的影响[J].生物物理学报.1991,7(4)：524-529.
[8]Chobanian JV, Tall AR, Brecher PI. Inter-action between unilamellar egg yolk lecithin vesi-cles and human high density lipoprotein[J]. Biochemistry.1979,18:180-187
[9]Damen J, Regts J, Scherphof G. Transfer and exchange of phospholipid between small uni-lamellar liposomes and rat plasma high densitylipoproteins:Dependence on cholesterol contentand phospholipid composition[J]. Biochim Biophys Acta.1981,665:538-545.
[10]Semple SC, Chonn A, Cullis PR. Influence of cholesterol on theassociation of plasma proteins with liposomes[J]. Biochemistry.1996,35:2521-2525.
[11]Dos Santos N, Allen C, Doppen AM, et al. Influence of poly(ethylene glycol) grafting density and polymer length on liposomes:Relating plasma circulation lifetimes to protein binding[J]. Biochim Biophys Acta.2007,1768:1367-1377.
[12]Liu ZH. Thermo sensitivity of polymeric liposomes[J]. Chim Pharm J.1997,32(10):593-595.
[13]Kim MS, Kim JS, You YH, et al. Development and optimization of a novel oral controlled delivery system for tamsulosin hydrochloride using response surface methodology[J]. International Journal of Pharmaceutics.2007,341:97-104.
[1]Muller RH, Karsten M, Sven G. Solid lipid nanoparticles (SLN) for controlled drug delivery—a review of the state or the art. Eur J Pharm Biopharm 2000;50:161-177.
[2]S.A. Wissinga, O. Kayserb, R.H. Mu'ller, Solid lipid nanoparticles for parenteral drug delivery. Advanced Drug Delivery Reviews 56 (2004) 1257-1272.
[3]王建新,张志荣.固体脂质纳米粒的研究进展[J].中国药学杂志,2001,36(2)：73-76.
[4]Siekmann B, Westesen K, Melt-homogenized solid lipid nanoparticles stabilized by the nonionic surfactant tyloxapol. I. Preparation and particle size determination. Pharm. Phartelmacol. Lett.1994, (3):194-197.
[5]Ahlin P, Kristl J, Smid-Kobar J. Optimization of procedure parameters and physical stability of solid lipid nanoparticles in dispersions, Acta Pharm,1998, (48):257-267.
[6]Muller RH, Mader K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery-a review of the state of the art [J]. Eur J Pharm Biopharm,2000,50(1):161-177
[7]Mehnert W, Madex K. Solid lipid nanoparticles:production characterization and applications [J]. Adv Drug Deliv Rev,2001,47(2/3):165-196
[8]陈玲,周建平.固体脂质纳米粒研究新进展[J].药学进展,2003,27(6)：354-358
[9]孙学慧,郭涛,何进等.大蒜油固体脂质纳米粒的制备工艺研究[J]解放军药学学报,2006,22(5)：336-340
[10]Siekmann B, Westesen K. Investigation on solid lipid nanoparticles prepared by precipitation in O/W emulsion [J]. Eur J Pharm Biopharm,1996,43 (2):104.
[11]李姜晖,王柏.乳化蒸发法制备固体脂质纳米粒[J].药学进展,2008,32(3)：127-131
[12]韩静,唐星,巴德纯.降香挥发油固体脂质纳米粒的制备工艺研究[J].沈阳药科大学学报,2004,21(4)：257-260
[13]李娟,张锦琳.褪黑素固体脂质纳米粒的制备及理化性质[J].中国医药工业杂志,2007,38(4)：277-281
[14]Siekmann B, Westesen K, Melt-homogenized solid lipid nanoparticles stabilized by the nonionic surfactant tyloxapol. Ⅰ. Preparation and particle size determination. Pharm. Phartelmacol. Lett,1994, (3):194-197.
[15]Uner M, Wissing SA, Yener G, Muller RH. Influence of surfactants on the physical stability of solid lipid nanoparticle (SLN) formulations. Pharmazie,2004,59(4):331-332.
[16]李晨睿,蒋学华,袁牧等.口服葛根素固体脂质纳米粒的制备[J].华西药学杂志,2007,22(4)：378-380
[17]Westesen K, Bunjes H, Koch MHJ, Physicochemical charcterization of lipid nanoparticles and evaluation of their drug loanding capacity and sustained release potential. J Control Release,1997, 48(2-3):223-236.
[18]Eldem T, Speiser F, Altorfer H. Polymorphic behavior of sprayed lipid micropellets and its evaluation by differential scanning calorimetry and scanning electron microscopy. Pharm Res,1991, 8(2):178-184
[19]Westesen K, Siekmann B, Koch M.H.J. Investigations on the physical state of lipid nanoparticles by synchroton radiation X-ray diffraction. Int. J. Pharm.1993,93(1):189-199.
[1]Awasthi VD, Garcia D, Goins BA, et al. Circulation and biodistribution profiles of long-circulating PEG-liposomes of various sizes in rabbits[J]. Int J Pharm.2003,253:121-131.
[2]Yang T, Cui FD, Choi MK, et al. Enhanced solubility and stability of PEGylated liposomal paclitaxel: In vitro and in vivo evaluation[J]. International Journal of Pharmaceutics.2007,338:317-326
[3]Napper DH. Polymeric stabilization of colloidal dispersions[M]. Academic:New York.1983.
[4]Drummond DC, Meyer O, Hong K, et al. Optimizing liposomes for delivery of chemothera-peutic agents to solid tumors[J]. Pharmacol Rev.1999,51:691-703.
[5]Semple SC, Chonn A, Cullis PR, Influence of cholesterol on the association of plasma-proteins with liposomes. Biochemistry,1996,35:2521-2525
[6]Beugin S, Edwards K, Karlsson G, Ollivon M, LesieurS, New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and poly(ethylene glycol)-cholesterol conjugates. Biophys. J.,1998, 74:3198-3210
[7]Beugin-Deroo S, Ollivon M, Lesieur S, Bilayer stability and impermeability of nonionic surfactant vesicles sterically stabilized by PEG-Cholesterol conjugates. J. Colloid Interf. Sci.,1998,202: 324-333
[8]Bradley AJ, Devine DV, Ansell SM, Janzen J, Brooks DE, Inhibition of liposome-induced complement activation by incorporated poly(ethylene glycol)-lipids. Arch. Biochem. Biophys.,1998,357:185-194
[9]Janzen J, Song X, Brooks DE, Interfacial thickness of liposomes containing poly(ethylene glycol)-cholesterol from electrophoresis. Biophys. J.,1996,70:313-320
[10]Yuda T, Maruyama K, Iwatsuru M, Prolongation of liposome circulation time by various derivatives of polyethyleneglycols. Biol. Pharm. Bull.,1996,19:1347-1351
[11]Ishiwata H, Vertut-Doi A, Hirose T, Miyajima K, Physical-chemistry characteristics and biodistribution of poly(ethylene glycol)-coated liposomes using poly(oxyethylene) cholesteryl ether. Chem. Pharm. Bull.,1995,43:1005-1011
[12]Webb MS, Saxon D, Wong FMP, Lim HJ, Wang Z, et al., Comparison of different hydrophobic anchors conjugated to poly(ethylene glycol)-effects on the pharmacokinetics of liposomal vincristine. Biochim. Biophys. Acta,1998,1372:272-282
[13]Shimada K, Kamps JM, Regts J, Ikeda K, Shiozawa T, Hirota S, Scherphof G, Biodistribution of liposomes containing synthetic galactose-terminated diacylglyceryl-poly(ethyleneglycol)s. Biochim. Biophys. Acta,1997,1326:329-341
[14]Ishiwata H, Sato SB, Kobayashi S, Oku M, Vertut-Doi A, Miyajima K, Polyethylene glycol) derivative of cholesterol reduces binding step of liposome uptake by murine macrophage-like cell line J774 and human hepatoma cell line HepG2. Chem. Pharm. Bull,1998,46:1907-1913
[15]Janzen J, Song X, Brooks DE, Interfacial thickness of liposomes containing poly(ethylene glycol)-cholesterol from electrophoresis. Biophys. J.,1996,70:313-320
[16]于志江,陈旭,欧阳藩.冷冻干燥技术在基因工程药物中的应用.生物加工过程,2005,3(2)：58-63
[17]Crowe LM, Crowe JH, Method for preserving liposomes, US patent 4,857,319,1989
[1]Maruy K., Holmberg E., Kennel S.J., Characterization of in vivo immunoliposome targeting to pulmonary endothelium. J. Pharm. Sci.,1990,79:978-984
[2]吴岩,毕力夫,流式细胞计量术的原理.内蒙古医学院学报,2002,24：203-207
[3]Williams S.S., Alosco T.R., Mayhew E., Lasic D.D., Martin F.J., Bankert R.B., Arrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes Cancer Res.,1993,53:964-3967
[4]Kazuo Maruyama, Tomoko Takizawa. Targeting of novel immunoliposomes modified with amphipathic poly (ethylene glycol)s conjugated at their distal terminals to monoclonal antibody. Biochim. Biophys. Acta.,1995,1234:74-80
[5]Tina V., Peter H., Thomas M., Rolf M, Roland E. K. Targeting of immunoliposomes to endothelial cells using a single-chain Fv fragment directed against human endoglin (CD 105). Biochim. Biophys. Acta,2004,1663:158-166
[6]Vertut-Doi A., Ishiwata H., Miyajima K., Binding and uptake of liposomes containing a poly (ethylene glycol) derivative of cholesterol (stealth liposomes) by the macrophage cell line J774:influence of PEG content and its molecular weight. Biochim. Biophys. Acta.,1996,278:19-28
[7]Park J.W., Kirpotin D.B., Hong K., Shalaby R., Shao Y., Nielsen U.B., Marks J.D., Papahadjopoulos D., Benz C.C., Tumor targeting using anti-her2 immunoliposomes, J. Control. Release,2001,74 (1-3): 95-113
[8]陆伟跃,刘敏,潘俊,等.叶酸脂质体制备及对Hela细胞靶向作用.上海医科大学学报,2000,27(1)：4-8
[9]Kessner S, Krause A, Rothe U, Bendas G, Investigation of the cellular uptake of E-Selection-targeted immunoliposomes by activated human endothelial cells. Biochem Biophys Acta.,2001,1514:177-190
[10]Maitani Y, Kawano K, Yamada K, et al, Efficiency of liposomes surface-modified with soybean-derived sterylglucoside as a liver targeting carrisd in HepG2 cells. J Control Released,2001, 75:381-389
[11]Malinin VS, Haque ME, Lentz BR, The rate of lipid transfer during fusion depends on the structure of fluorescent lipid probes:a new chain-labeled lipid transfer probe pair. Biochemistry,2001,40 (28): 8292-8299
[12]柯爱武,聚乙二醇修饰免疫脂质体研究进展,国外医学预防诊断治疗用生物制品分册,2004,27(4)：170-175
[13]Torchilin VP. Structure and design of polymeric surfactant-based drug delivery systems [J]. J Control Release 2001,73:137-172.
[1]陈洁,邱利焱,胡新敏等.多烯紫杉醇固体分散体的制备和体内外研究[J].中国药学杂志,2003,42(22)：1717-1722.
[2]丛宁,于治国,邱利焱等.RP-HPLC法测定大鼠血浆中多烯紫杉醇的含量[J].沈阳药科大学学报,2008,25(4)：304-308.
[3]Mallikarjuna RB, Chakraborty A, Srinivasu MK, et al. A stability-indicating HPLC assay method for docetaxel [J]. J Pharm Biomed Anal,2006 (41):676-681.
[4]陈永法,龚明涛,张钧寿等.紫杉醇冻干纳米乳在大鼠体内的药动学[J].中国天然药物,2005,3：370-372.
[5]张学农,唐丽华,阎雪莹等.紫杉醇冻干注射剂在大鼠体内的药代动力学[J].中成药,2005,27(5)：556-558.
[6]周卫,吕琦,翁帼英.紫杉醇脂质体在大鼠体内的药动学[J].中国药科大学学报,2000,31(6)：443-446.
[7]Takeuchi H, Kojima H, Yamamoto H, et al., Evaluation of circulation profiles of liposomes coated with hydrophilic polymers having different molecular weights in rats, J Control Release,2001,75 (1-2):83-91
[8]Poon R, Y. In:F. Fox and T. H. Connor (eds.), Biotechnology International:International Developments in the Biotechnology Industry, pp.113-128. San Francisco:Universal Medical Press (1997)
[1]Lasic DD, Papahadjopoulos D, Liposomes revisited. Science,1995,267:1275-1276
[2]Papahadjopoulos D, Allen TM, Gabizon A, et al. Sterically stabilized liposomes:improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci USA,1991,88:11460-11464
[3]Klibanov AL, Maruyama K, Torchilin VP, et al. Amphipathic polyethyleneglycols effectively prolong the circulation times of liposomes. FEBS Lett,1990,268:235-237
[4]Harrington KJ, Lewanski CR, Stewart JSW, Liposomes as vehicles for targeted therapy of cancer. Part 1:Preclinical development. Clin. Oncol (R Coll Radiol),2000,12:2-15
[5]高坤,陈凤菊,孙进等.高效液相色谱-质谱联用法测定大鼠血浆中多西他赛的含量.沈阳药科大学学报,200,25(6)：462-466.
[6]Z Xu,L Chen,W Gu, et al. The performance of docetaxel-loaded solid lipid nanoparticles targeted to hepatocellular carcinoma. Biomaterials,2009,30:226-232.
[2]De Jong M, Breeman WA, Bernard BF, Bakker WH, Schaar M, VanGameren A, et al. [177Lu-DOTA0,Tyr3] octreotate for somatostatinreceptor-targeted radionuclide therapy. Int J Cancer 92:628-633
[3]马寄晓,叶大铸.奥曲肽及其类似物用于肿瘤治疗的进展,国外医学.放射医学核医学分册,29(2)：79-83
[4]David Raben, Murray Stackhouse, Donald J. Buchsbaum, Galeena Mikheeva, M. B. Khazaeli, et al. 2207 Genetic induction of the gastrin releasing peptide receptor on tumor cells for radiolabeled peptide binding, International Journal of Radiation Oncology*Biology*Physics,36 (1):378-389.
[5]Stackhouse MA. Buchsbaum DJ. Kancharla SR. Specific membrane receptor gene expression targeted with radiolabeled peptide employing the erbB-2 and DF3 promoter elements in adenoviral vectors. Cancer Gene Therapy,6 (3):209-19
[6]Buck E. Rogers, Donald J. Buchsbaum, Richard L. Kirkman,et al. In Vivo Localization of [111In]-DTPA-D-Phel-Octreotide to HumanOvarian Tumor Xenografts Induced to Express the SomatostatinReceptor Subtype 2 Using an Adenoviral Vector1. Clinical Cancer Research,5:383-393
[7]H. Shimura, K. Haraguchi, A. Miyazaki, T. Endo, T. Onaya, Iodide uptake and experimental 131I-therapy in transplanted undifferentiatedthyroid cancer cells expressing the Na/I-symporter gene,Endocrinology 138:4493-4496
[8]Zhang, L. Sharma, S. Hershman, J. M. Iodide sensitizes genetically modified non-small cell lung cancer cells to ionizing radiation. Cancer Gene Therapy; Jan2006,13 (1), p74-81
[9]Achim Wenzel, Geeta Upadhyay, Thomas L. Schmitt and Ulrich Loos, Iodination of proteins in TPO transfected thyroid cancer cells is independent of NIS. Molecular & Cellular Endocrinology,213 (1):99-108
[10]Lasic DD, Papahadjopoulos D, Liposomes revisited. Science,1995,267:1275-1276
[11]Papahadjopoulos D, Allen TM, Gabizon A, et al. Sterically stabilized liposomes:improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci USA,1991,88:11460-11464
[12]Klibanov AL, Maruyama K, Torchilin VP, et al. Amphipathic polyethyleneglycols effectively prolong the circulation times of liposomes. FEBS Lett,1990,268:235-237
[13]Harrington KJ, Lewanski CR, Stewart JSW, Liposomes as vehicles for targeted therapy of cancer. Part 1:Preclinical development. Clin. Oncol (R Coll Radiol),2000,12:2-15
[14]A. T. M. Vaughan, A. R. Bradwell, P. W. Dykes and P. Anderson, Illusions of tumour killing using radiolabelled antibodies, The Lancet,327, (8496):1492-1493
[15]Ko AH, Tempero MA. Treatment of metastatic pancreatic cancer, JNatl Compr Cancer Netw, 2005,3:627-36
[16]Jo Whelan, Beyond PEGylation, DDT,10 (5):301.
[17]Dadachova E. Bouzahzah B. Zuckier LS. Pestell RG. Rhenium-188 as an alternative to Iodine-131 for treatment of breast tumors expressing the sodium/iodide symporter (NIS), Nuclear Medicine & Biology,29 (1):13-18.
[18]Boyd M. Cunningham SH. Brown MM. Mairs RJ. Wheldon TE. Noradrenalin transporter gene transfer for radiation cell kill by 1311 meta-iodobenzylguanidine, Gene Therapy.6 (6):1147-52
[19]Juweid ME, Hajjar G, Swayne LC, et al. Phase 1/Ⅱ trial of 131I-MN-14F(ab)2:anti carcinoembryonic antigen monoclonal antibody in the treatment of patients with metastatic medullary thyroid carcinoma.Cancer,85 (6):1828-1840
[20]Sengelov L, von der Maase H. Radiotherapy in bladder cancer. Radiother Oncol,52 (1):1-14
[21]Lesley Wilsona, Marie Boyd, et al. Application of Targeted Radiotherapy/GeneTherapy to Bladder Cancer Cell Lines, European Urology 47:250-256
[22]Shuji Tanada, Hajime Murata, Yasuhito Sasaki, et al. Labeling of Phosphorothioate Antisense Oligonucleotideswith Yttrium-90, Nuclear Medicine & Biology,26:239-243
[23]Guvakova M. A., Yakubov L. A., Vlodavsky I., Tonkinson J. L. andStein C. A. Phosphorothioate oligodeoxynucleotides bind to basic fibroblast growth factor, inhibit its binding to cell surfacereceptors, and remove it from low affinity binding sites on extracellular matrix, Biol. Chem. 270:2620-2627
[24]Ho P. T. C. and Parkinson D. R. Antisense oligonucleotides astherapeutics for malignant diseases. Semin. Oncol,24:187-202
[25]徐玉清,文雪梅。多西他赛磁微球的制备。哈尔滨医科大学学报,2005,39(6)：537-539
[26]lmmordino ML, Bmsa P, Arpicco S, et al. Preparation characterization cytotoxicity and pharmacokinetics of liposomes containing docetaxel. J Controlled Release,2003,91(4):417-429
[27]杜振新,卢秀莲,李大涛等。一种含有多西他赛的脂肪乳剂及其制备方法：中国,200510084055,6[P]。2005-12-21
[28]张先林。抗肿瘤药多西紫杉醇制剂的应用研究近况。药学进展,2006,30：516-520
[1]Papahadjopoulos D, Allen T, Gabizon A, et al, Sterically stabilized liposomes:improvements in pharmacokinetics and anti-tumor efficacy. Proc. Natl. Acad. Sci. USA,1991,88:11460-11464
[2]Anees A, Karnachi, Mansoor A.Khan. Box-behnken design for the optimization of formulation variables of indomethacin coprecipitates with polymer mixtures[J]. International Journal of Pharmaceutics.1996,131:9-17.
[3]Mohammad TH, Mahmoud S, Soliman, et al. Optimization and characterization of controlled release multi-particulate beads coated with starch acetate[J]. International Journal of Pharmaceutics.2005, 294:89-101.
[4]吴伟,崔光华.星点设计-效应面优化法及其在药学中的应用[J].国外医学药学分册.2000,27(5)：292-297.
[5]赵荣生,候新朴,严宝霞.脂质体载体材料卵磷脂的制备及质量标准研究[J].中国现代应用药学杂志.2001,1(18)：39-41.
[6]Gabizon, Papahadjopoulos D. The role of surface charge and hydrophilic groups on liposome clearance in vivo[J]. Biochim Biophys Acta.1992,1103(1):94-100.
[7]胡兰荣,董志伟.掺入胆固醇和阴离子磷脂对阿霉素免疫脂质体性能的影响[J].生物物理学报.1991,7(4)：524-529.
[8]Chobanian JV, Tall AR, Brecher PI. Inter-action between unilamellar egg yolk lecithin vesi-cles and human high density lipoprotein[J]. Biochemistry.1979,18:180-187
[9]Damen J, Regts J, Scherphof G. Transfer and exchange of phospholipid between small uni-lamellar liposomes and rat plasma high densitylipoproteins:Dependence on cholesterol contentand phospholipid composition[J]. Biochim Biophys Acta.1981,665:538-545.
[10]Semple SC, Chonn A, Cullis PR. Influence of cholesterol on theassociation of plasma proteins with liposomes[J]. Biochemistry.1996,35:2521-2525.
[11]Dos Santos N, Allen C, Doppen AM, et al. Influence of poly(ethylene glycol) grafting density and polymer length on liposomes:Relating plasma circulation lifetimes to protein binding[J]. Biochim Biophys Acta.2007,1768:1367-1377.
[12]Liu ZH. Thermo sensitivity of polymeric liposomes[J]. Chim Pharm J.1997,32(10):593-595.
[13]Kim MS, Kim JS, You YH, et al. Development and optimization of a novel oral controlled delivery system for tamsulosin hydrochloride using response surface methodology[J]. International Journal of Pharmaceutics.2007,341:97-104.
[1]Muller RH, Karsten M, Sven G. Solid lipid nanoparticles (SLN) for controlled drug delivery—a review of the state or the art. Eur J Pharm Biopharm 2000;50:161-177.
[2]S.A. Wissinga, O. Kayserb, R.H. Mu'ller, Solid lipid nanoparticles for parenteral drug delivery. Advanced Drug Delivery Reviews 56 (2004) 1257-1272.
[3]王建新,张志荣.固体脂质纳米粒的研究进展[J].中国药学杂志,2001,36(2)：73-76.
[4]Siekmann B, Westesen K, Melt-homogenized solid lipid nanoparticles stabilized by the nonionic surfactant tyloxapol. I. Preparation and particle size determination. Pharm. Phartelmacol. Lett.1994, (3):194-197.
[5]Ahlin P, Kristl J, Smid-Kobar J. Optimization of procedure parameters and physical stability of solid lipid nanoparticles in dispersions, Acta Pharm,1998, (48):257-267.
[6]Muller RH, Mader K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery-a review of the state of the art [J]. Eur J Pharm Biopharm,2000,50(1):161-177
[7]Mehnert W, Madex K. Solid lipid nanoparticles:production characterization and applications [J]. Adv Drug Deliv Rev,2001,47(2/3):165-196
[8]陈玲,周建平.固体脂质纳米粒研究新进展[J].药学进展,2003,27(6)：354-358
[9]孙学慧,郭涛,何进等.大蒜油固体脂质纳米粒的制备工艺研究[J]解放军药学学报,2006,22(5)：336-340
[10]Siekmann B, Westesen K. Investigation on solid lipid nanoparticles prepared by precipitation in O/W emulsion [J]. Eur J Pharm Biopharm,1996,43 (2):104.
[11]李姜晖,王柏.乳化蒸发法制备固体脂质纳米粒[J].药学进展,2008,32(3)：127-131
[12]韩静,唐星,巴德纯.降香挥发油固体脂质纳米粒的制备工艺研究[J].沈阳药科大学学报,2004,21(4)：257-260
[13]李娟,张锦琳.褪黑素固体脂质纳米粒的制备及理化性质[J].中国医药工业杂志,2007,38(4)：277-281
[14]Siekmann B, Westesen K, Melt-homogenized solid lipid nanoparticles stabilized by the nonionic surfactant tyloxapol. Ⅰ. Preparation and particle size determination. Pharm. Phartelmacol. Lett,1994, (3):194-197.
[15]Uner M, Wissing SA, Yener G, Muller RH. Influence of surfactants on the physical stability of solid lipid nanoparticle (SLN) formulations. Pharmazie,2004,59(4):331-332.
[16]李晨睿,蒋学华,袁牧等.口服葛根素固体脂质纳米粒的制备[J].华西药学杂志,2007,22(4)：378-380
[17]Westesen K, Bunjes H, Koch MHJ, Physicochemical charcterization of lipid nanoparticles and evaluation of their drug loanding capacity and sustained release potential. J Control Release,1997, 48(2-3):223-236.
[18]Eldem T, Speiser F, Altorfer H. Polymorphic behavior of sprayed lipid micropellets and its evaluation by differential scanning calorimetry and scanning electron microscopy. Pharm Res,1991, 8(2):178-184
[19]Westesen K, Siekmann B, Koch M.H.J. Investigations on the physical state of lipid nanoparticles by synchroton radiation X-ray diffraction. Int. J. Pharm.1993,93(1):189-199.
[1]Awasthi VD, Garcia D, Goins BA, et al. Circulation and biodistribution profiles of long-circulating PEG-liposomes of various sizes in rabbits[J]. Int J Pharm.2003,253:121-131.
[2]Yang T, Cui FD, Choi MK, et al. Enhanced solubility and stability of PEGylated liposomal paclitaxel: In vitro and in vivo evaluation[J]. International Journal of Pharmaceutics.2007,338:317-326
[3]Napper DH. Polymeric stabilization of colloidal dispersions[M]. Academic:New York.1983.
[4]Drummond DC, Meyer O, Hong K, et al. Optimizing liposomes for delivery of chemothera-peutic agents to solid tumors[J]. Pharmacol Rev.1999,51:691-703.
[5]Semple SC, Chonn A, Cullis PR, Influence of cholesterol on the association of plasma-proteins with liposomes. Biochemistry,1996,35:2521-2525
[6]Beugin S, Edwards K, Karlsson G, Ollivon M, LesieurS, New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and poly(ethylene glycol)-cholesterol conjugates. Biophys. J.,1998, 74:3198-3210
[7]Beugin-Deroo S, Ollivon M, Lesieur S, Bilayer stability and impermeability of nonionic surfactant vesicles sterically stabilized by PEG-Cholesterol conjugates. J. Colloid Interf. Sci.,1998,202: 324-333
[8]Bradley AJ, Devine DV, Ansell SM, Janzen J, Brooks DE, Inhibition of liposome-induced complement activation by incorporated poly(ethylene glycol)-lipids. Arch. Biochem. Biophys.,1998,357:185-194
[9]Janzen J, Song X, Brooks DE, Interfacial thickness of liposomes containing poly(ethylene glycol)-cholesterol from electrophoresis. Biophys. J.,1996,70:313-320
[10]Yuda T, Maruyama K, Iwatsuru M, Prolongation of liposome circulation time by various derivatives of polyethyleneglycols. Biol. Pharm. Bull.,1996,19:1347-1351
[11]Ishiwata H, Vertut-Doi A, Hirose T, Miyajima K, Physical-chemistry characteristics and biodistribution of poly(ethylene glycol)-coated liposomes using poly(oxyethylene) cholesteryl ether. Chem. Pharm. Bull.,1995,43:1005-1011
[12]Webb MS, Saxon D, Wong FMP, Lim HJ, Wang Z, et al., Comparison of different hydrophobic anchors conjugated to poly(ethylene glycol)-effects on the pharmacokinetics of liposomal vincristine. Biochim. Biophys. Acta,1998,1372:272-282
[13]Shimada K, Kamps JM, Regts J, Ikeda K, Shiozawa T, Hirota S, Scherphof G, Biodistribution of liposomes containing synthetic galactose-terminated diacylglyceryl-poly(ethyleneglycol)s. Biochim. Biophys. Acta,1997,1326:329-341
[14]Ishiwata H, Sato SB, Kobayashi S, Oku M, Vertut-Doi A, Miyajima K, Polyethylene glycol) derivative of cholesterol reduces binding step of liposome uptake by murine macrophage-like cell line J774 and human hepatoma cell line HepG2. Chem. Pharm. Bull,1998,46:1907-1913
[15]Janzen J, Song X, Brooks DE, Interfacial thickness of liposomes containing poly(ethylene glycol)-cholesterol from electrophoresis. Biophys. J.,1996,70:313-320
[16]于志江,陈旭,欧阳藩.冷冻干燥技术在基因工程药物中的应用.生物加工过程,2005,3(2)：58-63
[17]Crowe LM, Crowe JH, Method for preserving liposomes, US patent 4,857,319,1989
[1]Maruy K., Holmberg E., Kennel S.J., Characterization of in vivo immunoliposome targeting to pulmonary endothelium. J. Pharm. Sci.,1990,79:978-984
[2]吴岩,毕力夫,流式细胞计量术的原理.内蒙古医学院学报,2002,24：203-207
[3]Williams S.S., Alosco T.R., Mayhew E., Lasic D.D., Martin F.J., Bankert R.B., Arrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes Cancer Res.,1993,53:964-3967
[4]Kazuo Maruyama, Tomoko Takizawa. Targeting of novel immunoliposomes modified with amphipathic poly (ethylene glycol)s conjugated at their distal terminals to monoclonal antibody. Biochim. Biophys. Acta.,1995,1234:74-80
[5]Tina V., Peter H., Thomas M., Rolf M, Roland E. K. Targeting of immunoliposomes to endothelial cells using a single-chain Fv fragment directed against human endoglin (CD 105). Biochim. Biophys. Acta,2004,1663:158-166
[6]Vertut-Doi A., Ishiwata H., Miyajima K., Binding and uptake of liposomes containing a poly (ethylene glycol) derivative of cholesterol (stealth liposomes) by the macrophage cell line J774:influence of PEG content and its molecular weight. Biochim. Biophys. Acta.,1996,278:19-28
[7]Park J.W., Kirpotin D.B., Hong K., Shalaby R., Shao Y., Nielsen U.B., Marks J.D., Papahadjopoulos D., Benz C.C., Tumor targeting using anti-her2 immunoliposomes, J. Control. Release,2001,74 (1-3): 95-113
[8]陆伟跃,刘敏,潘俊,等.叶酸脂质体制备及对Hela细胞靶向作用.上海医科大学学报,2000,27(1)：4-8
[9]Kessner S, Krause A, Rothe U, Bendas G, Investigation of the cellular uptake of E-Selection-targeted immunoliposomes by activated human endothelial cells. Biochem Biophys Acta.,2001,1514:177-190
[10]Maitani Y, Kawano K, Yamada K, et al, Efficiency of liposomes surface-modified with soybean-derived sterylglucoside as a liver targeting carrisd in HepG2 cells. J Control Released,2001, 75:381-389
[11]Malinin VS, Haque ME, Lentz BR, The rate of lipid transfer during fusion depends on the structure of fluorescent lipid probes:a new chain-labeled lipid transfer probe pair. Biochemistry,2001,40 (28): 8292-8299
[12]柯爱武,聚乙二醇修饰免疫脂质体研究进展,国外医学预防诊断治疗用生物制品分册,2004,27(4)：170-175
[13]Torchilin VP. Structure and design of polymeric surfactant-based drug delivery systems [J]. J Control Release 2001,73:137-172.
[1]陈洁,邱利焱,胡新敏等.多烯紫杉醇固体分散体的制备和体内外研究[J].中国药学杂志,2003,42(22)：1717-1722.
[2]丛宁,于治国,邱利焱等.RP-HPLC法测定大鼠血浆中多烯紫杉醇的含量[J].沈阳药科大学学报,2008,25(4)：304-308.
[3]Mallikarjuna RB, Chakraborty A, Srinivasu MK, et al. A stability-indicating HPLC assay method for docetaxel [J]. J Pharm Biomed Anal,2006 (41):676-681.
[4]陈永法,龚明涛,张钧寿等.紫杉醇冻干纳米乳在大鼠体内的药动学[J].中国天然药物,2005,3：370-372.
[5]张学农,唐丽华,阎雪莹等.紫杉醇冻干注射剂在大鼠体内的药代动力学[J].中成药,2005,27(5)：556-558.
[6]周卫,吕琦,翁帼英.紫杉醇脂质体在大鼠体内的药动学[J].中国药科大学学报,2000,31(6)：443-446.
[7]Takeuchi H, Kojima H, Yamamoto H, et al., Evaluation of circulation profiles of liposomes coated with hydrophilic polymers having different molecular weights in rats, J Control Release,2001,75 (1-2):83-91
[8]Poon R, Y. In:F. Fox and T. H. Connor (eds.), Biotechnology International:International Developments in the Biotechnology Industry, pp.113-128. San Francisco:Universal Medical Press (1997)
[1]Lasic DD, Papahadjopoulos D, Liposomes revisited. Science,1995,267:1275-1276
[2]Papahadjopoulos D, Allen TM, Gabizon A, et al. Sterically stabilized liposomes:improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci USA,1991,88:11460-11464
[3]Klibanov AL, Maruyama K, Torchilin VP, et al. Amphipathic polyethyleneglycols effectively prolong the circulation times of liposomes. FEBS Lett,1990,268:235-237
[4]Harrington KJ, Lewanski CR, Stewart JSW, Liposomes as vehicles for targeted therapy of cancer. Part 1:Preclinical development. Clin. Oncol (R Coll Radiol),2000,12:2-15
[5]高坤,陈凤菊,孙进等.高效液相色谱-质谱联用法测定大鼠血浆中多西他赛的含量.沈阳药科大学学报,200,25(6)：462-466.
[6]Z Xu,L Chen,W Gu, et al. The performance of docetaxel-loaded solid lipid nanoparticles targeted to hepatocellular carcinoma. Biomaterials,2009,30:226-232.