"Synthesizing Safety Data on Novel Intravaginal Formulations: A Comprehensive Scoping Review of In vivo and In vitro Research".

Abstract

Background and objectives: Intravaginal drug delivery systems are gaining attention for their potential to treat local and systemic gynaecological conditions, offering advantages such as bypassing hepatic first-pass metabolism and improved bioavailability. However, the safety evaluation of these novel formulations remains inconsistent, with limited regulatory guidance. This scoping review aims to consolidate data from in vivo and in vitro safety studies to support the design of standardized safety protocols for future intravaginal formulations.

Materials and methods: A systematic data search was conducted using PubMed and Scopus (2009-2024) data base following PRISMA-ScR guidelines. Eligible studies were included after data screening by individual reviewers. Study selection, data extraction, and charting were performed using a pre-defined protocol registered on the Open Science Framework.

Results: A total of 77 studies were included, comprising 64 in vivo and 13 in vitro studies. Rabbit was the frequently used animal model, while HeLa and normal vaginal epithelial cells were predominant in cell-based assays. Key safety endpoints evaluated included vaginal irritation, systemic toxicity, cytotoxicity, and cytokine expression. A wide range of formulations was assessed, including gels, rings, suppositories, and hydrogels.

Conclusions: This review highlights the need for harmonized safety assessment protocols for intravaginal formulations. By mapping current practices and models used in preclinical research, this work offers a foundation for researchers and regulators to develop more robust and standardized safety evaluation frameworks.