Gelatin-Based Microspheres for Sustained Ketoprofen Delivery in Difficult-to-Heal Wounds

Chronic wounds remain a significant clinical challenge due to persistent inflammation and impaired tissue repair. Anti-inflammatory agents play a pivotal role in wound management by reducing excessive inflammation, preventing further tissue damage, and creating a microenvironment conducive to healing. Among them, Ketoprofen, a non-steroidal anti-inflammatory drug, is effective in modulating inflammation. However, its systemic administration is associated with adverse effects, highlighting the need for localized and controlled delivery systems. Gelatin-based carriers provide important advantages, including biocompatibility, biodegradability, low immunogenicity, cost-effectiveness, and the ease of chemical modification to tailor drug release profiles. In this pioneering study, gelatin-based microspheres crosslinked with tannic acid were developed to achieve sustained topical release of Ketoprofen. The microparticle system was produced through the single water-in-oil emulsification process and optimized by varying homogenization speed, crosslinking time, and molar ratio. Morphological, physicochemical, functional, and biological characterizations were conducted. The optimized formulation yielded spherical microspheres (5-35 µm) with high crosslinking efficiency and a controlled drug release profile over time. COX inhibition assays provided preliminary evidence that released Ketoprofen-retained inhibitory activity under the assay conditions, while cytocompatibility tests supported the short-term compatibility of the system within the tested concentration range. A qualitative wound-model test provided preliminary evidence of powder hydration, film formation, and macroscopic retention. Overall, tannic acid-crosslinked gelatin microspheres represent a biocompatible and promising platform for localized drug delivery of non-steroidal anti-inflammatory in wound management.