Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Int J Pharm. 2021 Jun 1;602:120665. doi: 10.1016/j.ijpharm.2021.120665. Epub 2021 Apr 30.
In the absence of an effective vaccine, vaginal microbicides are essential for preventing the sexual transmission of HIV to women. Antiretroviral vaginal films have emerged as promising choices, especially those offering mucoadhesivity and controlled drug release. Tenofovir-loaded bilayer films based on Eudragit® L100 (EL100) and a biopolymer - gum arabic, karaya gum, pectin or tragacanth gum - were developed in a single-stage process. Cytotoxicity studies in three human cell lines indicated no toxicity of the excipients at the concentrations tested. Raman spectroscopy and SEM confirmed the formation of the two layers and their anchoring. Texture analysis showed no major differences between the batches. The swelling of the film is conditioned by its biopolymer nature and by the amount of EL100, which acts as structuring agent thus enhancing swelling. Tragacanth gum-based batches showed high mucoadhesion regardless the amount of EL100. The controlled release of Tenofovir in simulated vaginal fluid was faster in the presence of simulated seminal fluid due to the dissolution of EL100. Films containing 400 mg of EL100 and tragacanth gum are promising candidates for future studies, as they could sexually safeguard women from HIV for at least one week and ensure greater protection during intercourse.
在缺乏有效疫苗的情况下，阴道杀微生物剂对于预防艾滋病毒通过性途径传播给女性至关重要。抗逆转录病毒阴道膜已成为有前途的选择，特别是那些具有粘膜粘附性和控制药物释放的膜。基于 Eudragit® L100（EL100）和生物聚合物-阿拉伯胶、瓜尔胶、果胶或黄蓍胶的载有替诺福韦的双层膜是在单步工艺中开发的。在三种人细胞系中的细胞毒性研究表明，在测试浓度下赋形剂没有毒性。拉曼光谱和 SEM 证实了两层的形成及其固定。纹理分析表明，批次之间没有明显差异。由于其生物聚合物性质和 EL100 的量，薄膜的溶胀受到调节，EL100 作为结构剂，从而增强了溶胀。基于黄蓍胶的批次无论 EL100 的含量如何，都具有高粘膜粘附性。由于 EL100 的溶解，在存在模拟精液的情况下，替诺福韦在模拟阴道液中的释放更快。含有 400mg EL100 和黄蓍胶的薄膜是未来研究的有前途的候选物，因为它们可以使女性在至少一周内免受艾滋病毒的性传播，并在性交期间提供更大的保护。
