Semi-solid gels function as physical barriers to human immunodeficiency virus transport in vitro
Semi-solid gels function as physical barriers to human immunodeficiency virus transport in vitro
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DOI：
10.1016/j.antiviral.2010.08.006
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发表时间：
2010-11-01
影响因子：
7.6
通讯作者：
Katz, David F.
中科院分区：
文献类型：
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作者：
Lai, Bonnie E.;Geonnotti, Anthony R.;Katz, David F.
阴道凝胶可能在性传播过程中充当艾滋病毒的物理屏障。然而，这种影响的程度和意义尚不清楚。在艾滋病毒从男性到女性的性传播过程中，含有感染性艾滋病毒的精液存在于女性下生殖道内。如果先前已将局部凝胶应用于阴道上皮，则病毒粒子在到达脆弱组织之前必须穿过凝胶层。这种额外的屏障可能会影响抗艾滋病毒杀菌剂凝胶和安慰剂的功能。为了更好地了解 HIV 在凝胶中的转运，我们：（1）量化了 HIV 病毒粒子在半固体递送载体内的扩散系数； (2) 测试 Transwell 系统中薄凝胶层的屏障功能。在杀菌剂临床试验中用作安慰剂的两种凝胶，羟乙基纤维素 (HEC) 和甲基纤维素 (MC)，被发现可阻碍 HIV 体外转运。 HIV病毒体在未稀释的HEC和MC中的扩散系数分别为4+/-2×10(-12)和7+/-1×10(-12)cm(2)/s。这些值几乎比 HIV 在水中的扩散系数低 10,000 倍。在扩散系数上升到比水中低两个数量级之前，需要大量的凝胶稀释（80%：稀释剂/凝胶，v/v）。在 Transwell 系统中，大约 150 微米厚的凝胶层减少了 HIV 的转运。孵育 0、4 和 8 小时后，突破 Transwell 膜的 HIV 数量呈对数减少。凝胶作为艾滋病毒从精液转运至组织的物理屏障的能力还取决于其在上皮上的分布以及阴道液或精液的稀释作用。这里的结果可以作为未来设计阻碍艾滋病毒传播的产品的基准。在设计和解释杀菌剂临床试验时应考虑安慰剂凝胶的潜在屏障功能。 (C) 2010 Elsevier B.V. 保留所有权利。
Vaginal gels may act as physical barriers to HIV during sexual transmission. However, the extent and significance of this effect are not well understood. During male-to-female sexual transmission of HIV, semen containing infectious HIV is present within the lower female reproductive tract. In cases where a topical gel has previously been applied to the vaginal epithelium, virions must move through gel layers before reaching vulnerable tissue. This additional barrier could affect the functioning of anti-HIV microbicide gels and placebos. To better understand HIV transport in gels, we: (1) quantified diffusion coefficients of HIV virions within semi-solid delivery vehicles; and (2) tested the barrier functioning of thin gel layers in a Transwell system. Two gels used as placebos in microbicides clinical trials, hydroxyethyl cellulose (HEC) and methylcellulose (MC), were found to hinder HIV transport in vitro. The diffusion coefficients for HIV virions in undiluted HEC and MC were 4 +/- 2 x 10(-12) and 7 +/- 1 x 10(-12) cm(2)/s, respectively. These are almost 10,000 times lower than the diffusion coefficient for HIV in water. Substantial gel dilution (80%:diluent/gel, v/v) was required before diffusion coefficients rose to even two orders of magnitude lower than those in water. In the Transwell system, gel layers of approximately 150-mu m thickness reduced HIV transport. There was a log reduction in the amount of HIV that had breached the Transwell membrane after 0-, 4-, and 8-h incubations. The ability of a gel to function as a physical barrier to HIV transport from semen to tissue will also depend on its distribution over the epithelium and effects of dilution by vaginal fluids or semen. Results here can serve as a baseline for future design of products that act as barriers to HIV transmission. The potential barrier function of placebo gels should be considered in the design and interpretation of microbicides clinical trials. (C) 2010 Elsevier B.V. All rights reserved.