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Preclinical evaluation of alternative pharmaceutical delivery vehicles for paclitaxel

 

作者: Walter Loos,   Janos Szebeni,   Albert ten Tije,   Jaap Verweij,   Desirée van Zomeren,   Kyu-nung Chung,   Kees Nooter,   Gerrit Stoter,   Alex Sparreboom,  

 

期刊: Anti-Cancer Drugs  (OVID Available online 2002)
卷期: Volume 13, issue 7  

页码: 767-775

 

ISSN:0959-4973

 

年代: 2002

 

出版商: OVID

 

关键词: Cremophor EL;drug delivery vehicle;paclitaxel;solubilizer

 

数据来源: OVID

 

摘要:

New solubilizers, including Sorporol 230, Sorporol 120Ex, Aceporol 345-T, Aceporol 460 and Riciporol 335, as potential new delivery vehicles for paclitaxel were investigated, since recent studies have shown that the paclitaxel delivery vehicle Cremophor EL significantly alters the pharmacokinetics of paclitaxel. Cremophor EL and Tween 80 were used as a reference. As in the case of Cremophor EL, alteration of blood distribution of paclitaxel occurred in the presence of all tested vehicles. Also, no differences in the affinity of paclitaxel for the tested solubilizers was found during equilibrium dialysis experiments. The different vehicles could be distinguished by a different rate of esterase-mediated breakdown, which was correlated with the fatty acid content of the solubilizers. The activation of the complement cascade was less pronounced for all solubilizers, except Riciporol 335, compared to Cremophor EL. The strategies presented here provide the possibility to rapidly screen future candidate delivery vehicles with optimal characteristics for use as a solubilizer in clinical formulations of paclitaxel or other poorly water-soluble drugs.

 

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