Enhanced oral bioavailability of docetaxel by lecithin nanoparticles: preparation, in vitro, and in vivo evaluation.
Enhanced oral bioavailability of docetaxel by lecithin nanoparticles: preparation, in vitro, and in vivo evaluation.
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DOI：
10.2147/ijn.s32880
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发表时间：
2012
影响因子：
8
通讯作者：
Feng J
中科院分区：
文献类型：
--
作者：
Hu K;Cao S;Hu F;Feng J
本研究的目的是探讨卵磷脂纳米颗粒（LNs）在提高多西紫杉醇口服生物利用度方面的潜力。以水包油乳液为原料制备了多西他赛负载的DTX-LNs，并对其形貌、大小、zeta电位和包封效率进行了表征。采用透析袋法研究多西紫杉醇纳米颗粒的体外释放。采用Caco-2细胞单层进行DTX-LNs的体外渗透研究。在大鼠体内进行了生物利用度研究，并对口服DTX-LNs后的不同药代动力学参数进行了评估。结果表明，DTX-LNs的平均直径为360±8 nm，呈球形，表面光滑。DTX-LNs具有缓释特性，约80%的多西他赛在72小时内释放。多西紫杉醇通过Caco-2细胞单层从DTX-LNs的根尖向基底侧转运是多西紫杉醇溶液的2.14倍（0.15 × 10−5±0.016 × 10−5 cm/秒vs 0.07 × 10−5±0.003 × 10−5 cm/秒）。DTX-LNs的口服生物利用度是多西他赛溶液的3.65倍（8.75% vs 2.40%）。这些结果表明，DTX-LNs作为一种促进多西紫杉醇吸收的口服给药系统是有价值的。
The aim of this research work was to investigate the potential of lecithin nanoparticles (LNs) in improving the oral bioavailability of docetaxel. Docetaxel-loaded LNs (DTX-LNs) were prepared from oil-in-water emulsions and characterized in terms of morphology, size, zeta potential, and encapsulation efficiency. The in vitro release of docetaxel from the nanoparticles was studied by using dialysis bag method. Caco-2 cell monolayer was used for the in vitro permeation study of DTX-LNs. Bioavailability studies were conducted in rats and different pharmacokinetic parameters were evaluated after oral administration of DTX-LNs. The results showed that DTX-LNs had a mean diameter of 360 ± 8 nm and exhibited spherical shape with smooth surface under transmission electron microscopy. The DTX-LNs showed a sustained-release profile, with about 80% of docetaxel released within 72 hours. The apical to basolateral transport of docetaxel across the Caco-2 cell monolayer from the DTX-LNs was 2.14 times compared to that of the docetaxel solution (0.15 × 10−5 ± 0.016 × 10−5 cm/second versus 0.07 × 10−5 ± 0.003 × 10−5 cm/second). The oral bioavailability of the DTX-LNs was 3.65 times that of docetaxel solution (8.75% versus 2.40%). These results indicate that DTX-LNs were valuable as an oral drug delivery system to enhance the absorption of docetaxel.