ABSTRACT
A novel chitosan-based multifunctional nanoparticle (PY-CS-PLA) using cationic polylysine (PL) polymer and L-cysteine has been developed and investigated for the oral delivery of paclitaxel (PTX). As amphiphilic polymer, PY-CS-PLA presented good capability in self-assembling into spherical nanoparticle with mean size of 165â¯nm, and encapsulating PTX into the hydrophobic core. The encapsulated PTX was observed to be sustainedly released from the functionalized chitosan nanoparticle, and with a positive correlation to the pH value of the medium in the range of 1.2 to 7.4. The in vitro studies indicated that PY-CS-PLA/PTX could effectively enhance the cellular uptake of the PTX in Caco-2 cells. Pharmacokinetic result indicated that the oral bioavailability of PY-CS-PLA/PTX in rats was determined to be 5.63-fold to that of Taxol. Moreover, PY-CS-PLA/PTX improved the distribution of PTX in tumor site and presented better antitumor efficacy in Heps tumor-bearing mice and with less toxicity than other formulations. In conclusion, the PY-CS-PLA/PTX nanoparticle might be developed as a promising delivery vehicle for improving the oral bioavailability and therapeutic effect of hydrophobic antitumor drugs.