Abstract
BACKGROUND: The aim of this work was to develop a novel and feasible modification strategy by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD) for enhancing the biological transport efficiency of paclitaxel (PTX)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles. METHODS: PTX-loaded 2-HP-β-CD-modified PLGA nanoparticles (2-HP-β-CD/PLGA NPs) were prepared using the modified emulsion method. Nano-characteristics, drug release behavior, in vitro cytotoxicity, cellular uptake profiles and in vivo bio-behavior of the nanoparticles were then characterized. RESULTS: Compared with the plain PLGA NPs, 2-HP-β-CD/PLGA NPs exhibited smaller particle sizes (151.03±1.36 nm), increased entrapment efficiency (~49.12% increase) and sustained drug release. When added to A549 human lung cancer cells, compared with PLGA NPs, 2-HP-β-CD/PLGA NPs exhibited higher cytotoxicity in MTT assays and improved cellular uptake efficiency. Pharmacokinetic analysis showed that the AUC value of 2-HP-β-CD/PLGA NPs was 2.4-fold higher than commercial Taxol(®) and 1.7-fold higher than plain PLGA NPs. In biodistribution assays, 2-HP-β-CD/PLGA NPs exhibited excellent stability in the circulation. CONCLUSION: The results of this study suggest that the formulation that contains 2-HP-β-CD can prolong PTX release, enhance drug transport efficiency and serve as a potential tumor targeting system for PTX.