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

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. (C) 2011 Elsevier Ltd. All rights reserved.