Abstract | PURPOSE: 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:
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Authors | Ya Jin, Zimei Wu, Caibin Li, Weisai Zhou, John P Shaw, Bruce C Baguley, Jianping Liu, Wenli Zhang |
Journal | Pharmaceutical research
(Pharm Res)
Vol. 35
Issue 1
Pg. 13
(01 04 2018)
ISSN: 1573-904X [Electronic] United States |
PMID | 29302821
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)
- Antineoplastic Agents
- Delayed-Action Preparations
- Drug Carriers
- Micelles
- Phosphatidylethanolamines
- Amsacrine
- Vitamin E
- Polyethylene Glycols
- tocophersolan
- asulacrine
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Topics |
- Amsacrine
(analogs & derivatives, chemistry, pharmacokinetics, therapeutic use)
- Animals
- Antineoplastic Agents
(chemistry, pharmacokinetics, therapeutic use)
- Cell Culture Techniques
- Cell Survival
- Delayed-Action Preparations
- Drug Carriers
(chemistry)
- Drug Liberation
- Drug Stability
- Half-Life
- Humans
- MCF-7 Cells
- Male
- Micelles
- Nanoparticles
(chemistry)
- Particle Size
- Permeability
- Phosphatidylethanolamines
(chemistry)
- Polyethylene Glycols
(chemistry)
- Rats
- Rats, Sprague-Dawley
- Surface Properties
- Vitamin E
(chemistry)
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