title: Pharmacokinetics, biodistribution, efficacy and safety of N-octyl-O-sulfate chitosan micelles loaded with paclitaxel.
abstract: Paclitaxel (Taxol), PTX) is a promising anti-cancer drug and has been successfully used to treat a wide variety of cancers. Unfortunately, serious clinical side effects are associated with it, which are caused by PTX itself and non-aqueous vehicle containing Cremophor EL. Development of new formulation of PTX with better efficacy and fewer side effects is extremely urgent. In the present study, a N-octyl-O-sulfate chitosan (NOSC) micelle was developed and used as the delivery system for PTX. The pharmacokinetics, biodistribution, efficacy and safety of PTX-loaded NOSC micelles (PTX-M) were evaluated. The results showed that NOSC micelles had high drug loading capacity (69.9%) and entrapment efficiency (97.26%). The plasma AUC of PTX-M was 3.6-fold lower than that of Taxol; but the V(d) and CL of PTX-M were increased by 5.7 and 3.5-fold, respectively. Biodistribution study indicated that most of the PTX were distributed in liver, kidney, spleen, and lung and the longest retention effect was observed in the lung. Drug safety assessment studies including acute toxicity, hemolysis test, intravenous stimulation and injection anaphylaxis revealed that the PTX-M was safe for intravenous injection. Furthermore, the comparable antitumor efficacy of PTX-M and Taxol was observed at the same dose of 10 mg/kg in in vivo antitumor mice models inoculated with sarcoma180, enrich solid carcinoma (EC), hepatoma solidity (Heps), Lewis lung cancer cells and A-549 human lung cancer cells. These results clearly showed that PTX-M had the similar antitumor efficacy as Taxol, but significantly reduced the toxicity and improved the bioavailability of PTX.
authors: College of Pharmacy, China Pharmaceutical University, Nanjing, PR China.
authors: Can
authors: C
authors: Zhang
authors: Guowei
authors: G
authors: Qu
authors: Yingji
authors: Y
authors: Sun
authors: Xiaoli
authors: X
authors: Wu
authors: Zhong
authors: Z
authors: Yao
authors: Qinglong
authors: Q
authors: Guo
authors: Qilong
authors: Q
authors: Ding
authors: Shengtao
authors: S
authors: Yuan
authors: Zilong
authors: Z
authors: Shen
authors: Qineng
authors: Q
authors: Ping
authors: Huiping
authors: H
authors: Zhou
mesh_terms: D017738:Alkanesulfonic Acids; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D001672:Biocompatible Materials; D001682:Biological Availability; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D048271:Chitosan; D016503:Drug Delivery Systems; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy; D008297:Male; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012449:Safety; D012510:Sarcoma 180 / Q000188:drug therapy; D014018:Tissue Distribution
chemical_list: D017738:Alkanesulfonic Acids; D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D008823:Micelles; D048271:Chitosan; C042005:1-octanesulfonic acid; D017239:Paclitaxel