Efficient and effective chemotherapeutic methods designed to prevent the continuous spread of HIV/AIDS is essential to break the cycle of new infections. The use of condoms has been seen to be effective in prevention of HIV and STIs but its lack of use especially in vulnerable population is a deterrent to its overall success as a control method. Utilization of topical microbicide to curb the spread of HIV follows the current paradigm for HIV prevention in at risk individuals. The objective of this study was to develop and evaluate hyaluronic acid/palm oil-based organogel loaded with maraviroc (MRV) which would be released using hyaluronidase as the trigger for pre-exposure prophylaxis of HIV. The organogels had average globules size 581.8 ± 3.9 nm, and were stable after three freeze thaw cycles; the thermosensitive and HA sensitivity was achieved via incorporation of hyaluronic acid and dicaprylate esters in the organogel with thermogelation occurring at 34.1 °C. Artificial neural network was used to model and optimize mucin absorption and flux. These responses were predicted using the multilayer full feed forward (MFFF) and the multilayer normal feed forward (MNFF) neural networks. Optimized organogel showed the mucin adsorption and flux was 70.84% and 4.962 μg/cm2/min1/2, hence MRV was adequately released via triggers of temperature and HA. The MRV organogel showed inhibition HIV − 1 via TZM-bl indicator cells. Compared to control HeLa cells without any treatment, MRV organogel was not cytotoxic for 14 days in vitro. These data highlight the potential use of hyaluronic acid/palm oil-based organogel for vaginal delivery of anti-HIV microbicides. This can serve as a template for more studies on such formulations in the area of HIV prevention.

中文翻译：

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使用人工神经网络开发触发敏感的透明质酸/棕榈油基有机凝胶，用于体外释放HIV / AIDS杀微生物剂

旨在防止HIV / AIDS持续传播的有效，有效的化学治疗方法对于打破新的感染周期至关重要。人们已经看到使用避孕套可以有效地预防艾滋病毒和性传播疾病，但避孕套的缺乏使用，特别是在脆弱人群中，阻碍了其作为控制手段的整体成功。利用局部杀微生物剂来遏制艾滋病毒的传播遵循了目前在高危人群中预防艾滋病毒的范例。这项研究的目的是开发和评估载有maraviroc（MRV）的透明质酸/棕榈油基有机凝胶，使用透明质酸酶作为HIV暴露前预防的触发因素将其释放。有机凝胶的平均小球尺寸为581.8±3.9 nm，经过三个冻融循环后保持稳定。热敏性和HA敏感性是通过在有机凝胶中加入透明质酸和二辛酸酯来实现的，在34.1°C时发生热胶凝。人工神经网络用于建模和优化粘蛋白的吸收和通量。使用多层完全前馈（MFFF）和多层正常前馈（MNFF）神经网络预测了这些响应。优化的有机凝胶显示粘蛋白的吸附和通量为70.84％和4.962μg/ cm2 / min1 / 2，因此通过触发温度和HA可以充分释放MRV。MRV有机凝胶通过TZM-b1指示细胞显示出HIV-1抑制作用。与未经任何处理的对照HeLa细胞相比，MRV有机凝胶在体外14天没有细胞毒性。这些数据突出说明了透明质酸/棕榈油基有机凝胶在抗艾滋病毒杀菌剂的阴道输送中的潜在用途。这可以作为在HIV预防领域中对此类制剂进行更多研究的模板。