COMPARATIVE STUDY
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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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±1.9nm, and high zata potential of -44.2±3.9mV. 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 12mg/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.

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