pH-dependent interactions of indinavir and lipids in nanoparticlies and their ability to entrap a solute
pH-dependent interactions of indinavir and lipids in nanoparticlies and their ability to entrap a solute
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DOI：
10.1002/jps.21020
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发表时间：
2008-02-01
影响因子：
3.8
通讯作者：
Ho, Rodney J. Y.
中科院分区：
文献类型：
--
作者：
Choi, Sung-Up;Bui, Tot;Ho, Rodney J. Y.
我们已经研究了由3：1的脂质-药物摩尔比组成的脂质-茚地那韦颗粒包封水性标记物钙黄绿素和抗HIV药物H-3-膦酰基甲氧基丙基腺嘌呤（PMPA）的能力。即使在与脂质-茚地那韦纳米颗粒缔合的高密度茚地那韦下，它们也形成封闭的脂质膜，该脂质膜允许将钙黄绿素和PMPA包封在水性隔室中。在中性pH下，几乎所有茚地那韦都被掺入脂质双层中，脂质相关茚地那韦可以解离，记录的半最大pH值为5.2至5.5。pH依赖性释放的茚地那韦没有影响钙黄绿素释放显着。然而，pH依赖性释放茚地那韦影响PMPA释放。通过降低pH值，在脂质双层中存在茚地那韦的情况下，PMPA释放增强。总的来说，这些数据表明掺入脂质颗粒中的茚地那韦提供（1）能够包封其它亲水性药物的稳定双层，（2）通过降低pH使茚地那韦（其是酸稳定的）从脂质膜解离的能力，和（3）能够增强水性内容物的pH依赖性释放。然而，pH依赖性释放的程度可能与水分子的电荷和大小有关。(C)2007 Wiley-Liss，Inc.和美国药剂师协会
We have investigated the ability of lipid-indinavir particles composed of 3-to- 1 lipid-drug molar ratio to encapsulate an aqueous marker calcein and anti-HIV drug H-3-phosphonylmethoxypropyl-adenine (PMPA). Even at a high density of indinavir associated to lipid-indinavir nanoparticles, they form an enclosed lipid membrane that allows encapsulation of calcein and PMPA in an aqueous compartment. At neutral pH, practically all indinavir was incorporated into lipid bilayer and lipid associated indinavir can be dissociated with half-maximum pH recorded between 5.2 and 5.5. pH-Dependent release of indinavir did not influence calcein release significantly. However, pH-dependent release of indinavir affected PMPA release. By lowering pH, PMPA release was enhanced in the presence of indinavir in the lipid bilayer. Collectively, these data indicate that indinavir incorporated in lipid particles provides (1) stable bilayers capable of encapsulating other hydrophilic drugs, (2) ability to dissociate indinavir (which is acid stable) from lipid membranes, by lowering the pH, and (3) enabling enhancement in pH-dependent release of aqueous contents. However, the degree of pH-dependent release could be related to the charge and size of an aqueous molecule. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.