Nano-encapsulation of azole antifungals: Potential applications to improve oral drug delivery
Nano-encapsulation of azole antifungals: Potential applications to improve oral drug delivery
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DOI：
10.1016/j.ijpharm.2005.05.027
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发表时间：
2005-09-14
影响因子：
5.8
通讯作者：
Khuller, GK
中科院分区：
文献类型：
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作者：
Pandey, R;Ahmad, Z;Khuller, GK
本研究旨在提高临床上两种重要的抗真菌药物克霉唑和益康唑的口服生物利用度。每种药物都被封装在合成聚合物（聚乳酸-共-乙交酯，PLG）或天然聚合物（用壳聚糖稳定的藻酸盐）的纳米颗粒中。纳米颗粒的制备通过乳化-溶剂-蒸发技术在PLG的情况下和通过阳离子诱导的受控凝胶化在藻酸盐的情况下。与PLG制剂（接近50%）相比，藻酸盐制剂的药物包封效率更好（>90%）。将制剂经口给予小鼠，并通过4种经验证的HPLC技术分析血浆中的药物。生物分布/药代动力学数据表明，与口服/静脉给药3-4小时内清除的未包封药物相比，每种制剂的药物控释持续5-6天。每种药物的相对和绝对生物利用度都有显著改善。此外，The。在组织（肺，.肝和脾），而游离药物在12小时内被清除。总体而言，藻酸盐制剂似乎优于PLG制剂。结果强调了纳米技术的力量，使唑类抗真菌药物口服生物利用度提高的概念成为现实。(C)2005 Elsevier B. V.保留所有权利。
The present study was designed to improve the oral bioavailability of two clinically important antifungal drugs clotrimazole and econazole. Each drug was encapsulated in nanoparticles of a synthetic polymer (polylactide-co-glycolide, PLG) or a natural polymer (alginate stabilized with chitosan). The nanoparticles were prepared by the emulsion-solvent-evaporation technique in case of PLG and by the cation-induced controlled gelification in case of alginate. Drug encapsulation efficiency was better (>90%) for the alginate formulation compared with the PLG formulation (nearly 50%). The formulations were orally administered to mice and the drugs were analyzed in plasma by 4 validated HPLC technique. The biodistribution/pharmacokinetic data suggested that there was a controlled drug release for 5-6 days with each of the formulations, compared with unencapsulated drugs, which wer ,cleared within 3-4 h of oral/intravenous administration. There was a striking improvement in the relative and absolute bioavailability of each drug. Further, the. drugs were detected in the tissues (lungs,. liver and spleen) till 6-8 days in case of nanoparticles whereas free drugs were cleared by 12 h. Overall, the alginate formulation appeared to be better than the PLG formulation. The results emphasize the power of nanotechnology to make the concept of enhancement in oral bioavailability of azole antifungal drugs come to reality. (C) 2005 Elsevier B.V. All rights reserved.