Self-Assembled Methoxy Poly(Ethylene Glycol)-Cholesterol Micelles for Hydrophobic Drug Delivery

• Published in: Journal of pharmaceutical sciences Vol. 102; no. 3; pp. 1054 - 1062
• Main Authors: Yu, Yiyi, He, Yingju, Xu, Bei, He, Zhiyao, Zhang, Ying, Chen, Yan, Yang, Yang, Xie, Yongmei, Zheng, Yu, He, Gu, He, Jun, Song, Xiangrong
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.03.2013; Wiley Subscription Services, Inc., A Wiley Company; Elsevier Limited
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; calorimetry(DSC); Cell Line, Tumor; Cell Proliferation - drug effects; cholesterol; Cholesterol - chemistry; cosolvent evaporation; docetaxel; Drug Carriers - chemistry; Drug Delivery Systems; Humans; Hydrophobic and Hydrophilic Interactions; hydrophobic drug; methoxy poly(ethylene glycol); micelle; Micelles; Neoplasms - drug therapy; Polyethylene Glycols - chemistry; polymers; stability; targeted drug delivery; Taxoids - administration & dosage; Taxoids - pharmacology; micelle; docetaxel; calorimetry(DSC); hydrophobic drug; cholesterol; targeted drug delivery; polymers; methoxy poly(ethylene glycol); stability; cosolvent evaporation
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.23418

To promote the application of methoxy poly(ethylene glycol)-cholesterol (mPEG—Chol), mPEG–Chol was used to prepare core-shell micelles encapsulating poorly water-soluble docetaxel (DTX-PM) by modified cosolvent evaporation method. Approaches to enhance DTX entrapment efficiency (EE) and minimize particle size were investigated in detail, including organic and aqueous phase composition, organic/aqueous phase ratio, and polymer concentration. In optimal formulation, micelles had higher EE (97.6%) and drug loading (4.76%) with the diameter of 13.76±0.68nm and polydispersity index of 0.213±0.006. Transmission electron microscopy (TEM) showed that the micelles were spherical, and differential scanning calorimetry (DSC) analysis proved that DTX was successfully entrapped into mPEG–Chol micelles. The in vitro cytotoxicity experiments displayed that blank micelles had no effect on the growth of SKOV-3, BXPC-3, A549, and HepG-2 cells, demonstrating that mPEG–Chol was one of the biocompatible biomaterials. The half inhibition concentration of DTX-PM on SKOV-3, BXPC-3, A549, and HepG-2 cells were 10.08, 7.6, 28.37, and 125.75ng/mL, respectively. DTX-PM had the similar antitumor activity to free DTX, indicating that mPEG–Chol was a promising micellar vector for hydrophobic drug delivery. In addition, this work provided a new and facile approach to prepare drug-loaded micelles with controllable performances. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1054–1062, 2013