Low molecular weight heparin-all-trans-retinoid acid conjugate as a drug carrier for combination cancer chemotherapy of paclitaxel and all-trans-retinoid acid

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• 作者：Lin Hou^a ; Ying Fan^a ; Jing Yao^a ; ^{yaoj3@163.com"" rel=""nofollow} ; Jianping Zhou^a ; ^{zhoujpcpu@126.com"" rel=""nofollow} ; Caocao Li^a ; Zhengjie Fang^a ; Qiang Zhang^b
• 关键词：Low molecular weight heparin ; Paclitaxel ; All-trans-retinoid acid ; Conjugates ; Self-assembled nanoparticles ; Combination therapy
• 刊名：Carbohydrate Polymers
• 出版年：2011
• 出版时间：30 August 2011
• 年：2011
• 卷：86
• 期：3
• 页码：1157-1166
• 全文大小：952 K

文摘

As a novel nanocarrier for simultaneous delivery of multiple anticancer drugs, low molecular weight heparin-all-trans-retinoid acid (ATRA) (LHR) conjugate was developed. Amphiphilic LHR conjugate had markedly lower anticoagulant activity, and could self-assemble to form nanoparticles for loading hydrophobic drugs. The critical aggregation concentrations of LHR conjugates were varied from 407 to 40 mg/L. Paclitaxel (PTX)-loaded LHR nanoparticles were prepared by the dialysis method, with particle sizes in the range of 228.0–108.9 nm. The maximum drug-loading was as much as 33.1 % with an entrapment efficiency of 93.1 % . They displayed enhanced PTX-induced cytotoxicity to HepG2 cells compared to PTX solution. Hemolysis and cytotoxicity studies showed that LHR conjugate was a safe material for intravenous administration. Moreover, the pharmacokinetic profiles indicated that PTX-loaded LHR nanoparticles contributed to an extended circulation of PTX and ATRA. These results suggest that PTX-loaded LHR nanoparticles can be considered as promising anticancer drug delivery system for combination chemotherapy.