Dynamics of HIV neutralization by a microbicide formulation layer: Biophysical fundamentals and transport theory
Dynamics of HIV neutralization by a microbicide formulation layer: Biophysical fundamentals and transport theory
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DOI：
10.1529/biophysj.106.086322
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发表时间：
2006-09-01
影响因子：
3.4
通讯作者：
Katz, David F.
中科院分区：
文献类型：
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作者：
Geonnotti, Anthony R.;Katz, David F.
局部杀微生物剂是一种新兴的艾滋病毒/艾滋病预防方式。杀微生物剂的生物功能性要求建立一种防止艾滋病毒传播的化学-物理屏障。屏障有效性来源于活性化合物及其递送系统的性质，但对这些性质如何转化为杀微生物剂功能知之甚少。我们开发了一个数学模型，模拟生物相关的运输和HIV-中和过程发生时，精液传播的病毒相互作用的杀微生物剂运载工具涂层上皮。该模型能够分析与媒介物相关的变量和抗HIV化合物特性如何影响杀微生物剂性能。结果表明，HIV中和是可实现的性交后涂层厚度; 100毫米。增加杀微生物剂浓度和效力加速病毒中和和减少感染性病毒通过涂层的渗透。限制病毒扩散的耐用载体结构可以提供显著的保护。我们的研究结果表明，需要将有效的活性成分与精心设计的制剂载体配对，并强调剂型在杀微生物剂有效性中的重要性。杀微生物剂制剂不仅可以用作药物递送载体，而且还可以用作病毒渗透的物理屏障。100 mm薄的涂层可完全中和病毒，支持未来使用杀微生物剂预防艾滋病毒传播。该模型可用作分析控制杀微生物剂功能的各种因素的工具。
Topical microbicides are an emerging HIV/AIDS prevention modality. Microbicide biofunctionality requires creation of a chemical-physical barrier against HIV transmission. Barrier effectiveness derives from properties of the active compound and its delivery system, but little is known about how these properties translate into microbicide functionality. We developed a mathematical model simulating biologically relevant transport and HIV-neutralization processes occurring when semen-borne virus interacts with a microbicide delivery vehicle coating epithelium. The model enables analysis of how vehicle-related variables, and anti-HIV compound characteristics, affect microbicide performance. Results suggest HIV neutralization is achievable with postcoital coating thicknesses; 100 mm. Increased microbicide concentration and potency hasten viral neutralization and diminish penetration of infectious virus through the coating layer. Durable vehicle structures that restrict viral diffusion could provide significant protection. Our findings demonstrate the need to pair potent active ingredients with well-engineered formulation vehicles, and highlight the importance of the dosage form in microbicide effectiveness. Microbicide formulations can function not only as drug delivery vehicles, but also as physical barriers to viral penetration. Total viral neutralization with 100-mm-thin coating layers supports future microbicide use against HIV transmission. This model can be used as a tool to analyze diverse factors that govern microbicide functionality.