In Situ Forming Injectable Gels: A Novel Approach for Controlled Drug Delivery—Polymers, Mechanisms, and Pharmaceutical Applications

Abstract

In situ forming injectable gels have emerged as a promising platform in advanced drug delivery systems, offering the ability to transform from a liquid state into a semi-solid gel upon administration. This unique sol–gel transition enables the formation of a localized drug depot, facilitating sustained and controlled release of therapeutic agents. These systems are triggered by physiological stimuli such as temperature, pH, ionic strength, and solvent exchange. A wide range of natural and synthetic polymers, including poloxamers, chitosan, sodium alginate, and poly(lactic-co-glycolic acid), are utilized in their formulation. The present review provides a comprehensive discussion on the mechanisms of gel formation, polymer selection, formulation strategies, characterization techniques, and diverse pharmaceutical applications. Furthermore, key challenges such as burst release, sterility concerns, scale-up limitations, and regulatory barriers are critically analyzed. Emerging trends, including smart polymers, nanogel integration, and artificial intelligence-driven formulation design, are also highlighted. Overall, in situ forming gels represent a versatile and innovative approach for enhancing therapeutic efficacy and patient compliance in parenteral drug delivery. Keywords: In situ forming gel, Injectable gel, Controlled drug delivery, Sol–gel transition, Thermosensitive polymers, pH-sensitive polymers, Ion-activated gelation, Poly(lactic-co-glycolic acid), Parenteral drug delivery, Sustained release systems