Fotouh Bassam, Kyser Anthony J, Frieboes Hermann B
Department of Bioengineering, University of Louisville, Louisville, KY, USA; School of Interdisciplinary and Graduate Studies, University of Louisville, Louisville, KY, USA.
Department of Bioengineering, University of Louisville, Louisville, KY, USA.
J Control Release. 2025 Aug 10;384:113924. doi: 10.1016/j.jconrel.2025.113924. Epub 2025 Jun 2.
Intravaginal drug and therapeutic delivery targeting diseases in the female reproductive tract is advantageous, yet presents significant challenges due to unique anatomical features, cyclic variations, and a complex microbial ecosystem. Disruption of the intricate vaginal environment due to dysbiosis or infection can decrease immune protection and lead to infertility and pregnancy complications. A variety of intravaginal drug delivery systems (DDS) including creams, gels, suppositories, tablets, rings, and films have been developed to address these conditions. However, relying solely on empirical methods to design and evaluate DDS composition and geometry, as well as dosing regimens, would be costly and time intensive. To address these challenges, mathematical modeling has recently emerged as a complementary tool to systematically evaluate intravaginal DDS performance as a function of drug diffusion, reactions, and biomechanical interactions. This review summarizes how the application of mass conservation and the integration of mechanistic and empirical methods can offer insight into DDS pharmacokinetics and pharmacodynamics. Models describing first-order kinetics, microbial interactions, formulation optimization, rheological behavior, and interactions with the vaginal environment are critically evaluated. It is shown that these models can systematically evaluate how various physical phenomena such as diffusion, swelling, dilution, surface slip, and mechanical compression interact to shape spatiotemporal patterns of drug release, permeability, and microbial dynamics. Challenges and limitations of current approaches as well as emerging technologies are discussed, with the goal to provide insight into how mathematical modeling could benefit the development of effective intravaginal therapies addressing female reproductive tract diseases.
针对女性生殖道疾病的阴道内药物和治疗递送具有优势，但由于独特的解剖特征、周期性变化和复杂的微生物生态系统，也带来了重大挑战。由于生态失调或感染导致的复杂阴道环境破坏会降低免疫保护，并导致不孕和妊娠并发症。为解决这些问题，人们开发了多种阴道内给药系统（DDS），包括乳膏、凝胶、栓剂、片剂、环和薄膜。然而，仅依靠经验方法来设计和评估DDS的组成、几何形状以及给药方案，将既昂贵又耗时。为应对这些挑战，数学建模最近已成为一种补充工具，用于系统地评估阴道内DDS作为药物扩散、反应和生物力学相互作用函数的性能。本综述总结了质量守恒的应用以及机理方法和经验方法的整合如何能够深入了解DDS的药代动力学和药效学。对描述一级动力学、微生物相互作用、制剂优化、流变行为以及与阴道环境相互作用的模型进行了批判性评估。结果表明，这些模型可以系统地评估扩散、溶胀、稀释、表面滑移和机械压缩等各种物理现象如何相互作用，以形成药物释放、渗透性和微生物动力学的时空模式。讨论了当前方法的挑战和局限性以及新兴技术，目的是深入了解数学建模如何能够有益于开发针对女性生殖道疾病的有效阴道内疗法。
