Formulation and evaluation of a thermosensitive in-situ gel for sustained delivery of Remdesivir

Abstract

The global outbreak of the COVID-19 pandemic has significantly intensified the need for effective antiviral therapies that can be administered efficiently and with minimal side effects. Remdesivir (RDV), a broad-spectrum antiviral agent, has demonstrated considerable efficacy against SARS-CoV-2, the virus responsible for COVID-19. Despite its therapeutic potential, RDV’s clinical application has been predominantly limited to intravenous administration, which poses challenges such as systemic toxicity, limited patient compliance, and the need for hospital-based care. Furthermore, the lack of effective ocular or localized formulations restricts its utility in treating viral infections at other anatomical sites. To address these challenges, this research investigates the formulation and evaluation of a thermosensitive in-situ gel designed for the sustained delivery of RDV. The gel is based on a poly (DHSe/PEG/PPG urethane) polymer matrix, which exhibits a sol-to-gel transition in response to physiological temperature (around 35-37 °C). This transition allows the formulation to be administered as a liquid and subsequently form a gel depot in situ, thereby enhancing drug retention at the site of action and enabling controlled release over an extended period. The in-situ gel was characterized through various In vitro and In vivo studies, including rheological analysis, drug release kinetics, cytotoxicity assessment, and ocular retention studies in animal models.