Ya Jin1, Zimei Wu2, Caibin Li1, Weisai Zhou1, John P Shaw2, Bruce C Baguley3, Jianping Liu4, Wenli Zhang5. 1. Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China. 2. School of Pharmacy, University of Auckland, Private Bag, Auckland, 92019, New Zealand. 3. Auckland Cancer Society Research Centre, University of Auckland, Private Bag, Auckland, 92019, New Zealand. 4. Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China. jianpingliu1293@163.com. 5. Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China. zwllz@163.com.
Abstract
PURPOSE: To enhance therapeutic efficacy and prevent phlebitis caused by Asulacrine (ASL) precipitation post intravenous injection, ASL-loaded hybrid micelles with size below 40 nm were developed to improve drug retention and tumor penetration. METHODS: ASL-micelles were prepared using different weight ratios of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethyleneglycol-2000 (DSPE-PEG2000) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymers. Stability of micelles was optimized in terms of critical micelle concentration (CMC) and drug release properties. The encapsulation efficiency (EE) and drug loading were determined using an established dialysis-mathematic fitting method. Multicellular spheroids (MCTS) penetration and cytotoxicity were investigated on MCF-7 cell line. Pharmacokinetics of ASL-micelles was evaluated in rats with ASL-solution as control. RESULTS: The ASL-micelles prepared with DSPE-PEG2000 and TPGS (1:1, w/w) exhibited small size (~18.5 nm), higher EE (~94.12%), better sustained in vitro drug release with lower CMC which may be ascribed to the interaction between drug and carriers. Compared to free ASL, ASL-micelles showed better MCTS penetration capacity and more potent cytotoxicity. Pharmacokinetic studies demonstrated that the half-life and AUC values of ASL-micelles were approximately 1.37-fold and 3.49-fold greater than that of free ASL. CONCLUSIONS: The optimized DSPE-PEG2000/TPGS micelles could serve as a promising vehicle to improve drug retention and penetration in tumor.
PURPOSE: To enhance therapeutic efficacy and prevent phlebitis caused by Asulacrine (ASL) precipitation post intravenous injection, ASL-loaded hybrid micelles with size below 40 nm were developed to improve drug retention and tumor penetration. METHODS:ASL-micelles were prepared using different weight ratios of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethyleneglycol-2000 (DSPE-PEG2000) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymers. Stability of micelles was optimized in terms of critical micelle concentration (CMC) and drug release properties. The encapsulation efficiency (EE) and drug loading were determined using an established dialysis-mathematic fitting method. Multicellular spheroids (MCTS) penetration and cytotoxicity were investigated on MCF-7 cell line. Pharmacokinetics of ASL-micelles was evaluated in rats with ASL-solution as control. RESULTS: The ASL-micelles prepared with DSPE-PEG2000 and TPGS (1:1, w/w) exhibited small size (~18.5 nm), higher EE (~94.12%), better sustained in vitro drug release with lower CMC which may be ascribed to the interaction between drug and carriers. Compared to free ASL, ASL-micelles showed better MCTS penetration capacity and more potent cytotoxicity. Pharmacokinetic studies demonstrated that the half-life and AUC values of ASL-micelles were approximately 1.37-fold and 3.49-fold greater than that of free ASL. CONCLUSIONS: The optimized DSPE-PEG2000/TPGS micelles could serve as a promising vehicle to improve drug retention and penetration in tumor.
Entities:
Keywords:
CMC; asulacrine; drug retention; hybrid micelles; multicellular spheroids penetration
Authors: Wenli Zhang; Guangji Wang; James R Falconer; Bruce C Baguley; John P Shaw; Jianping Liu; Hongtao Xu; Esther See; Jianguo Sun; Jiye Aa; Zimei Wu Journal: Pharm Res Date: 2014-10-30 Impact factor: 4.200
Authors: Nabil A Alhakamy; Osama A Ahmed; Usama A Fahmy; Hani Z Asfour; Adel F Alghaith; Wael A Mahdi; Sultan Alshehri; Shadab Md Journal: Front Pharmacol Date: 2021-07-16 Impact factor: 5.810