Chemico-physical investigation of tenofovir loaded polymeric nanoparticles
Chemico-physical investigation of tenofovir loaded polymeric nanoparticles
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DOI：
10.1016/j.ijpharm.2012.07.070
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发表时间：
2012-10-15
影响因子：
5.8
通讯作者：
Ruozi, Barbara
中科院分区：
文献类型：
--
作者：
Belletti, Daniela;Tosi, Giovanni;Ruozi, Barbara
替诺福韦（PMPA）是一种无环核苷膦酸酯类似物，是目前最重要的HIV治疗药物之一。不幸的是，由于阴离子肾转运蛋白的饱和，几种不良反应与其静脉给药有关。为了改善药物的给药，将PMPA包埋到基于聚-（D，L-丙交酯-共-乙交酯）（PLGA）和/或壳聚糖（CH）的新型纳米载体中。研究了相对于文献中报道的PMPA纳米胶囊化的纳米颗粒（Nps）具有更有效的药物负载的制备策略。CH在水/油/水（W/O/W）Nps的第一内乳液中或在第二乳液期间在外相中加入。在第一内乳液中加入CH是最有前途的技术。Nps具有230 nm的Z-平均值、-3 mV的Z-电位和15的EE%，其比用PLGA Nps或CH Nps获得的高2.5-3倍。体外释放研究表明，在磷酸盐缓冲液（pH 7.4）中对药物释放的控制有限，而在酸性接受相中（pH 4.6）观察到初始突释效应，随后是缓慢的药物释放。这些结果表明，PLGA/CH Nps应该是一种有效的和有吸引力的抗HIV药物载体，用于研究细胞摄取和药物在靶细胞如巨噬细胞上的递送。(c)2012 Elsevier B. V.保留所有权利。
Tenofovir (PMPA), an acyclic nucleoside phosphonate analog, is one of the most important drugs used for the HIV treatment. Unfortunately, several adverse reactions are related to its i.v. administration owing to the saturation of an anionic renal transporter. In order to improve the drug administration, the PMPA was embedded into a new type of nanocarriers based on poly-(D,L-lactide-co-glycolide) (PLGA) and/or chitosan (CH). The strategies for the preparation of nanoparticles (Nps) with a more efficient drug loading respect to the one reported in the literature for PMPA nanoencapsulation were investigated. CH was added in the first inner emulsion or in the external phase during the second emulsion of water/oil/water (W/O/W) Nps. The addition of CH in the first inner emulsion was the most promising technique. The Nps have a Z-average of 230 nm, a Z-potential of -3 mV and an EE% of 15 that was 2.5-3 times higher than that obtained with PLGA Nps or CH Nps. In vitro release studies showed a limited control on drug release in phosphate buffer (pH 7.4) while an initial burst effect followed by a slow drug release was observed in acidic receiving phase (pH 4.6). These results suggest the PLGA/CH Nps should be an effective and attractive anti-HIV drug carrier to study the cellular uptake and drug delivery on target cells such as macrophages. (c) 2012 Elsevier B.V. All rights reserved.