Ekama Sabdat O, Ilomuanya Margaret O, Azubuike Chukwuemeka P, Bamidele Tajudeen A, Fowora Muinah A, Aina Oluwagbemiga O, Ezechi Oliver C, Igwilo Cecilia I
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, Lagos, Nigeria.
Clinical Sciences Department, Nigerian Institute of Medical Research, Lagos, Nigeria.
HIV AIDS (Auckl). 2021 Apr 8;13:399-413. doi: 10.2147/HIV.S291065. eCollection 2021.
To formulate and evaluate microspheres of the antiretroviral drugs maraviroc and tenofovir intended for a candidate vaginal microbicide and assess its effect on the vaginal lactic acid bacteria microflora.
Ionic gelation technique was used to formulate maraviroc and tenofovir microspheres with subsequent characterization. The effect of varying concentrations of the polymer, crosslinking agent and the curing time on the outcome variables viz: particle size, mucoadhesion and encapsulation efficiency were investigated. Lactic acid bacteria were isolated from the vagina of healthy women using standard microbiologic methods. The analysis of their 16S rRNA sequence data identified and strains which were assigned GenBank accession numbers. The efficacy of the microspheres on HIV-1BaL strain was evaluated using TZM-bl indicator cells.
The optimal maraviroc and tenofovir microspheres had particle sizes of (434.82 µm and 456.18 µm), mucoadhesion of (93.3% and 90%) and encapsulation efficiency (92.80% and 78.9%) respectively. Maraviroc release kinetics followed a zero-order model and tenofovir was released via Higuchi model. The assay of a 1 mg/mL suspension of the microspheres on the strains of and showed a viability of 93.9% and 89.7%, respectively. There was a statistically significant difference between the mean absorbance readings of the test agent and that of the positive control (P = 0.001). The microspheres elicited a progressive decline in HIV infectivity until at a concentration of 1 μg/mL.
The antiretroviral drugs loaded in the microspheres, had good mucoadhesion which is a potential for prolonged residence time in the vagina. The antiretroviral drugs were adequately released from the microspheres and showed efficacy against the HIV-1 BaL virus strain. There was no significant disruption in the growth of the lactic acid bacteria which constitute valuable bacteria microflora of the vagina.
制备并评估用于候选阴道杀菌剂的抗逆转录病毒药物马拉维若和替诺福韦的微球，并评估其对阴道乳酸菌微生物群的影响。
采用离子凝胶技术制备马拉维若和替诺福韦微球，并进行后续表征。研究了聚合物、交联剂浓度及固化时间对粒径、黏膜黏附性和包封率等结果变量的影响。使用标准微生物学方法从健康女性阴道中分离乳酸菌。对其16S rRNA序列数据的分析鉴定出了菌株，并给出了GenBank登录号。使用TZM-bl指示细胞评估微球对HIV-1BaL毒株的疗效。
最佳的马拉维若和替诺福韦微球粒径分别为（434.82 µm和456.18 µm），黏膜黏附性分别为（93.3%和90%），包封率分别为（92.80%和78.9%）。马拉维若的释放动力学遵循零级模型，替诺福韦通过Higuchi模型释放。微球1 mg/mL悬浮液对菌株和的检测显示存活率分别为93.9%和89.7%。测试剂与阳性对照的平均吸光度读数之间存在统计学显著差异（P = 0.001）。微球使HIV感染性逐渐下降，直至浓度达到1 μg/mL。
微球中负载的抗逆转录病毒药物具有良好的黏膜黏附性，这有可能延长其在阴道中的停留时间。抗逆转录病毒药物从微球中充分释放，并显示出对HIV-1 BaL病毒株的疗效。构成阴道重要细菌微生物群的乳酸菌生长未受到显著破坏。
