title: In vivo pharmacokinetics, biodistribution and antitumor effect of paclitaxel-loaded micelles based on α-tocopherol succinate-modified chitosan.
abstract: In our previous study, α-tocopherol succinate modified chitosan (CS-TOS) was synthesized and encapsulated paclitaxel (PTX) to form micelles. Preliminary study revealed that the CS-TOS was a potential micellar carrier for PTX. In this study, some further researches were done using Taxol formulation as the control to evaluate the micelle system deeply. In vitro cell experiments demonstrated that the cytotoxic effect of PTX-loaded CS-TOS micelles against MCF-7 cells was comparable with that of Taxol formulation, and the PTX-loaded micelles had excellent cellular uptake ability, which was in a time-dependent manner. The in vivo pharmacokinetic study in rats showed that the micelles prolonged the half-life and increased AUC of PTX than Taxol formulation. From biodistribution study, it was clear that for micelles, the drug concentrations in the liver and spleen were significantly higher than those of Taxol formulation, but much lower in the heart and kidney. Furthermore, the PTX-loaded micelles showed superior antitumor effect, but yielded less toxicity as indicated by the results of antitumor efficacy study and survival study in U14 tumor-bearing mice. These results suggested that CS-TOS micelles could be a potentially useful drug delivery system to improve the performance and safety of PTX.
authors.affiliation: a College of Chemistry & Chemical Engineering, Harbin Normal University , Harbin , China.
authors.forename: Na
authors.initials: N
authors.lastname: Liang
authors.affiliation: b Key Laboratory of Chemical Engineering Process & Technology for High-efficiency Conversion, College of Heilongjiang Province, Heilongjiang University , Harbin , China.|c School of Chemistry and Material Science, Heilongjiang University , Harbin , China , and.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Sun
authors.affiliation: d School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Juan
authors.initials: J
authors.lastname: Hong
authors.affiliation: d School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Jingzhuo
authors.initials: J
authors.lastname: Tian
authors.affiliation: d School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
authors.affiliation: d School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Fude
authors.initials: F
authors.lastname: Cui
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006207:Half-Life; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D019802:Succinic Acid / Q000737:chemistry*; D014018:Tissue Distribution / Q000502:physiology; D024502:alpha-Tocopherol / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D048271:Chitosan; D019802:Succinic Acid; D024502:alpha-Tocopherol; D017239:Paclitaxel
keywords: chitosan; micelle; paclitaxel; pharmacokinetics; α-Tocopherol succinate