Kangyu Zheng1,2, Xiangmei Liu3, Junfeng Ban1,2, Zeju Huang1,2, Jiaying Huang1,2, Xin Huang1,2, Haosen Luo1,2, Zhicong Chen1,2, Qingchun Xie1,2, Yanzhong Chen1,2, Zhufen Lu1,2. 1. Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China. 2. Guangdong Provincial Engineering Center of Topical Precision Drug Delivery System, Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China. 3. Guangzhou Quality Supervision and Testing Institute, Guangzhou, People's Republic of China.
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.
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.
Authors: Kandice R Levental; Hongmei Yu; Laura Kass; Johnathon N Lakins; Mikala Egeblad; Janine T Erler; Sheri F T Fong; Katalin Csiszar; Amato Giaccia; Wolfgang Weninger; Mitsuo Yamauchi; David L Gasser; Valerie M Weaver Journal: Cell Date: 2009-11-25 Impact factor: 41.582