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

摘要

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 40mg/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 PTXMoaded LHR nanoparticles can be considered as promising anticancer drug delivery system for combination chemotherapy.