Cysteine modified and bile salt based micelles: preparation and application as an oral delivery system for paclitaxel.
The aim of the present study is to construct a cysteine modified polyion complex micelles made of Pluronic F127-chitosan (PF127-CS), Pluronic F127-cysteine (PF127-cysteine) and sodium cholate (NaC) and to evaluate the potential of the micelles as an oral drug delivery system for paclitaxel. Systematic studies on physicochemical properties including size distribution, zeta-potential and morphology were conducted to validate the formation of micelle structure. Compared with Pluronic micelles, drug-loading capacity of PF127-CS/PF127-cysteine/NaC micelles was increased from 3.35% to 12.77%. Both the critical micelle concentration and the stability test confirmed that the PF127-CS/PF127-cysteine/NaC micelles were more stable in aqueous solution than sodium cholate micelles. Pharmacokinetic study demonstrated that when oral administration the area under the plasma concentration-time curve (AUC0-∞) and the absolute bioavailability of paclitaxel-loaded micelles were five times greater than that of the paclitaxel solution. In general, PF127-CS/PF127-cysteine/NaC micelles were proven to be a potential oral drug delivery system for paclitaxel.
Department of Pharmacy, Shandong Provincial Qian Foshan Hospital, Jinan, Shandong Province, China.
Wei
W
Xu
Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong Province 250012, China.
Xiaohui
X
Fan
Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong Province 250012, China.
Yanli
Y
Zhao
Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong Province 250012, China. Electronic address: cnlilingbing@yahoo.com.
Lingbing
L
Li
D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry*; D004337:Drug Carriers; D004355:Drug Stability; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics*; D020442:Poloxamer / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D020358:Sodium Cholate / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D013501:Surface-Active Agents; D020442:Poloxamer; D048271:Chitosan; D003545:Cysteine; D020358:Sodium Cholate; D017239:Paclitaxel
Cysteine modified; Micelles; Oral; Paclitaxel; Sodium cholate