Nanoemulsions as versatile formulations for paclitaxel delivery: Peroral and dermal delivery studies in rats
Nanoemulsions as versatile formulations for paclitaxel delivery: Peroral and dermal delivery studies in rats
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DOI：
10.1038/sj.jid.5700485
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发表时间：
2007-01-01
影响因子：
6.5
通讯作者：
Panchagnula, Ramesh
中科院分区：
文献类型：
--
作者：
Khandavilli, Sateesh;Panchagnula, Ramesh
银屑病的发病机制涉及表皮的角质形成细胞以及涉及皮肤深层的血管生成。因此，药物递送策略应该被定制以将紫杉醇（PCL）定位在两个层内。在这项研究中，为了实现PCL渗透到更深的皮肤层，同时最大限度地减少全身逃逸，配制纳米乳液（NE），并评价其体内药代动力学性能。此外，探索了相同的制剂用于提高PCL的口服生物利用度。经皮给药后，药物主要局限于较深的皮肤层，全身逃逸最少。当以NE口服给药时，PCL被迅速吸收，在30分钟内达到3.5 μ g/ml的稳态值，并且稳态水平持续长达18小时。这相当于绝对生物利用度为70.62%。D-α-生育酚聚乙二醇1，000琥珀酸酯和labrasol对P-糖蛋白外排的抑制将有助于提高PCL的口服生物利用度。本研究为大分子量亲脂性药物PCL在真皮中的定位提供了直接证据。此外，NE制剂将口服生物利用度显著提高至70%以上。所开发的NE制剂对于PCL的经口和经皮递送都是安全有效的。
Pathogenesis of psoriasis involves the keratinocytes in epidermis as well as the angiogenesis involving deeper skin layers. So, the drug delivery strategy should be customized to localize paclitaxel (PCL) inside both layers. In this investigation, in order to achieve penetration of PCL into deeper skin layers while minimizing the systemic escape, a nanoemulsion (NE) was formulated and evaluated its in vivo pharmacokinetic performance. Further, the same formulation was explored for peroral bioavailability enhancement of PCL. Upon dermal application, the drug was predominantly localized in deeper skin layers, with minimal systemic escape. When orally administered as NE, PCL was rapidly absorbed reaching a steady-state value of 3.5 mu g/ml in 30 minutes, and steady-state levels persisted up to 18 hours. This has amounted to an absolute bioavailability of 70.62%. Inhibition of P-glycoprotein efflux by D-alpha-tocopheryl polyethyleneglycol 1,000 succinate and labrasol would have contributed to the enhanced peroral bioavailability of PCL. This investigation provides direct evidence on the localization of large molecular weight, lipophilic drug, PCL, in dermis. Further, the NE formulation has enhanced the peroral bioavailability significantly to more than 70%. The developed NE formulation was safe and effective for both peroral and dermal delivery of PCL.