Development of pegylated liposomal vincristine using novel sulfobutyl ether cyclodextrin gradient: Is improved drug retention sufficient to surpass DSPE–PEG-induced drug leakage?
✍ Scribed by Jingxia Cui; Chunlei Li; Caixia Wang; Yanhui Li; Lan Zhang; Li Zhang; Xian Xiu; Yongfeng Li; Na Wei
- Book ID
- 102394699
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 396 KB
- Volume
- 100
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
The purpose of this study is to develop novel stable PEGylated liposome vincristine formulations with optimal antitumor efficacy. Vincristine could interact with negatively charged distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG), leading to rapid drug release from vesicles. To improve drug retention, vincristine was loaded into vesicles using sulfobutyl ether cyclodextrin (sbe-CD) as trapping agent. Despite that, vincristine could not form a precipitate with sbe-CD; the aggregation status of vincristine/sbe-CD inside vesicles must be complicated because drug retention was considerably improved in vivo. Theoretical consideration revealed that the release constant K equals to pA m k 1 k 2 /([H + ] i [sbe -] i V i ), which can be used to expound why increasing drug/lipid ratio induced decreased vincristine circulation half-life. The stabilization effect afforded by sbe-CD was sufficient to surpass DSPE-PEGinduced drug leakage, so PEGylated liposomal vincristine formulations with prolonged circulation half-life (t 1/2 : from 43.6 to 70.0 h) could be achieved, of which the formulation pLV-c-2.9-3 exhibited optimal antitumor effects and reduced toxicity. The strategy might be used to load other vinca alkaloids into PEGylated liposomes and improve their retention inside vesicles.