title: N-octyl-O-sulfate chitosan-modified liposomes for delivery of docetaxel: preparation, characterization, and pharmacokinetics.
abstract: 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.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Qu
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.forename: Lifang
authors.initials: L
authors.lastname: Yin
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004355:Drug Stability; D005452:Fluoresceins / Q000737:chemistry; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D010316:Particle Size; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005452:Fluoresceins; D008081:Liposomes; C528556:N-octyl-O-sulfate chitosan; D043823:Taxoids; D000077143:Docetaxel; D012710:Serum Albumin, Bovine; D048271:Chitosan; C007740:fluorexon