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Abstract
A novel micelle formulation of paclitaxel (PTX) has been prepared for the purpose of prolonging the blood circulation time as well as modifying the biodistribution of PTX in comparison to a current PTX formulation, Taxol injection. This work was designed to investigate the preparation, in vitro release, in vivo pharmacokinetics, and tissue distribution of PTX-loaded DOMC-FA (deoxycholic acid- O-carboxymethylated chitosan- folic acid conjugate) micellar system. The micelles were prepared by self-assemble method using amphiphilic DOMC-FA polymer and a hydrophobic anticancer drug, PTX. The resultant PTX-loaded micelles had a mean size of approximately 152 nm with narrow size distribution and a spherical shape. The in vitro release profiles indicated that the release of PTX from the micelles exhibited a sustained release behavior. Pharmacokinetic study revealed that DOMC-FA/PTX micelles exhibited higher AUC values and a prolonged residence time of drug in the blood circulation than that of Taxol injection. The PTX-loaded micelles increased the uptake of PTX in the spleen, lung, and liver, but decreased uptake in the heart and kidney in the tissue distribution study. These results suggested that the DOMC-FA micelles can prolong blood circulation time and modify the tissue distribution of PTX, and could provide a useful alternative dosage form for intravenous administration of PTX.