School of Pharmacy, Faculty of Science, University of Waterloo, Kitchener, Ontario, Canada.
Waterloo Institute for Nanotechnology, Waterloo, Ontario, Canada.
Nanotechnology. 2024 Sep 4;35(47). doi: 10.1088/1361-6528/ad7143.
Bacterial vaginosis (BV) is a common vaginal infection affecting millions of women. Vaginal anaerobic dysbiosis occurs whenspp., the dominant flora in healthy vagina is replaced by certain overgrown anaerobes, resulting in unpleasant symptoms such as vaginal discharge and odor. With a high recurrence rate, BV also severely impacts the overall quality of life of childbearing women by inducing preterm delivery and increasing the risks of pelvic inflammatory disease and sexually transmitted infections. Among various BV-associated bacteria,() has been identified as a primary pathogen since it has been isolated from almost all women carrying BV and exhibits higher virulence potential over other bacteria. When dealing with BV relapse, intravaginal drug delivery systems are superior to conventional oral antibiotic therapies in improving therapeutic efficacy owing to more effective drug dose, reduced drug resistance and minimized side effects such as stomach irritation. Traditional intravaginal drug administration generally involves solids, semi-solids and delivery devices inserted into the vaginal lumen to achieve sustained drug release. However, they are mostly designed for continuous drug release and are not preventative therapies, resulting in severe side effects caused by excess dosing. Stimuli-responsive systems that can release drug only when needed ('on-demand') can help diminish these negative side effects. Hence, we developed a bacteria-responsive liposomal platform for the prevention and treatment of BV. This platform demonstrated sustained drug release in the presence of vaginolysin, a toxin secreted specifically by. We prepared four liposome formulations and evaluated their responsiveness to. The results demonstrated that the liposome formulations could achieve cumulative drug release ranging from 46.7% to 51.8% over a 3-5 d period in response toand hardly any drug release in the presence of(), indicating the high specificity of the system. Overall, the bacteria-responsive drug release platform has great potential, since it will be the first time to realize sustained drug release stimulated by a specific pathogen for BV prevention and treatment. This on-demand therapy can potentially provide relief to the millions of women affected by BV.
细菌性阴道病（BV）是一种常见的阴道感染，影响着数百万女性。当阴道中占主导地位的菌群，如，被某些过度生长的厌氧菌取代时，就会发生阴道厌氧失调，导致阴道分泌物和异味等不愉快的症状。由于高复发率，BV 还会通过诱导早产和增加盆腔炎和性传播感染的风险，严重影响育龄妇女的整体生活质量。在各种与 BV 相关的细菌中，（）已被确定为主要病原体，因为它几乎存在于所有患有 BV 的女性中，并且比其他细菌具有更高的毒力潜力。在处理 BV 复发时，由于能够更有效地给药、降低耐药性和最小化如胃部刺激等副作用，阴道内药物输送系统优于传统的口服抗生素疗法来提高治疗效果。传统的阴道内药物给药通常涉及固体、半固体和插入阴道腔以实现持续药物释放的给药装置。然而，它们主要设计用于持续药物释放，而不是预防疗法，导致因过量给药而产生严重的副作用。只有在需要时才能够释放药物的（即按需）响应系统可以帮助减少这些负面副作用。因此，我们开发了一种用于预防和治疗 BV 的细菌响应脂质体平台。该平台在阴道溶素（一种专门由分泌的毒素）存在下表现出持续的药物释放。我们制备了四种脂质体配方并评估了它们对的响应性。结果表明，脂质体配方在 3-5 天的时间内可以实现从 46.7%到 51.8%的累积药物释放，而在存在（）时几乎没有药物释放，表明该系统具有很高的特异性。总的来说，这种细菌响应的药物释放平台具有很大的潜力，因为这将是首次实现由特定病原体刺激的用于 BV 预防和治疗的持续药物释放。这种按需治疗可能会为受 BV 影响的数百万女性带来缓解。
