Development and in vitro evaluation of chloroquine gels as microbicides against HIV-1 infection
Development and in vitro evaluation of chloroquine gels as microbicides against HIV-1 infection
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DOI：
10.1016/j.virol.2008.06.005
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发表时间：
2008-09-01
期刊：
影响因子：
3.7
通讯作者：
Augustijns, Patrick
中科院分区：
文献类型：
--
作者：
Brouwers, Joachim;Vermeire, Kurt;Augustijns, Patrick
候选杀微生物剂在资源贫乏国家的潜在成功将在很大程度上取决于其可获得性和成本。氯喹是一种廉价的抗疟疾药物，也具有抗艾滋病毒活性。本研究的目的是开发和表征一种保留其抗HIV-1活性的氯喹阴道制剂。含有非离子聚合物羟乙基纤维素的凝胶负载有浓度（0.3-30 mg/g）的氯喹的二磷酸盐，其比氯喹的典型体外抗HIV-1 IC 50值（约10 mg/g）高10（2）至10（4）倍。6 μ g/ml）。凝胶是透明且均匀的，并且显示出300 mOsm/kg的所有重量摩尔渗透压浓度、4.6的pH和1.4 Pa s的粘度。凝胶特性在40 ℃和75%相对湿度下保存至少3个月。重要的是，氯喹凝胶在体外表现出紧密依赖的抗HIV-1活性（平均IC 50为23 - 0.4 mg凝胶/ml），并且氯喹的内在活性不受制剂因素的影响。氯喹凝胶制剂的体外功效保证了该药物作为抗HIV-1杀微生物剂候选物的进一步测试。(C)2008年爱思唯尔公司All rights reserved.
The potential success of a microbicide candidate in resource-poor Countries will depend to a large extent on its availability and cost. Chloroquine is an inexpensive antimalarial drug that also exerts anti-HIV activity. The Purpose of this study was to develop and characterize a vaginal formulation for chloroquine with preservation of its anti-HIV-1 activity. Gels containing the nonionic polymer hydroxyethyl cellulose were loaded with concentrations of the diphosphate salt of chloroquine (0.3-30 mg/g), that were 10(2) to 10(4) fold higher than typical in vitro anti-HIV-1 IC50-values of chloroquine (ca. 6 mu g/ml). The gels were clear and homogeneous and displayed all osmolality of 300 mOsm/kg, a pH of 4.6 and a viscosity of 1.4 Pa s. Gel characteristics were preserved for at least 3 months at 40 degrees C and 75% relative humidity. Importantly, the chloroquine gels exerted a close-dependent anti-HIV-1 activity in vitro (mean IC50 from 23 to 0.4 mg gel/ml) and the intrinsic activity of chloroquine was not affected by formulation factors. The in vitro efficacy of the chloroquine gel formulations warrants further testing of this drug as an anti-HIV-1 microbicide candidate. (C) 2008 Elsevier Inc. All rights reserved.