N-octyl-O-sulfate chitosan-modified liposomes for delivery of docetaxel: Preparation,characterization, and pharmacokinetics

A N-octyl-O-sulfate chitosan (NOSC) anchored liposome system was developed as the carrier for antitumor drug, docetaxel (DTX). The physicochemical and pharmacokinetic properties of NOSC-modified DTX liposomes (NDLs) were evaluated compared with the conventional DTX liposomes (DLs) and commercial dosage form of DTX, Taxotere^®. The results showed that NDLs had DTX-loading rate of 3.41%, entrapment efficiency of 61.73%, narrow distributed particle size of 147.6 ± 1.9 nm, and high zata potential of −44.2 ± 3.9 mV. The decreased permeability of the liposome bilayer was evaluated by release behavior of calcein (CAL) from the internal phase of NOSC-modified CAL liposomes (NCLs) and enhanced stability of NDLs owed to shielding effect of sulfonic shell from adsorption by BSA. After i.v. administration at the dose of 12 mg/kg, a significant increase in the AUC, MRT, and T_1/2β (P < 0.05) was observed in NDLs group compared with DLs and Taxotere^® group. AUC_0–∞ of NDLs was 6.14 and 1.55 times higher than Taxotere^® and DLs, respectively, and MRT_0–∞ of NDLs was 5.77 and 1.37 times higher than Taxotere^® and DLs, respectively. All these results suggested that anchored liposomes could increase the stability of DTX in vitro and in vivo, as compared with conventional liposomes and Taxotere^®. Therefore, NOSC as a polymeric shell to liposomes was effective to enhance the stability of liposomes containing DTX.