Development and in vivo evaluation of a self-polymerizable tranilast-loaded silicone gel for scar modulation

Hypertrophic scars and keloids represent pathological outcomes of wound healing characterized by excessive collagen deposition and persistent myofibroblast activity, necessitating effective therapeutic intervention. In this study, a self-polymerizable one-component silicone gel loaded with tranilast was developed and evaluated in a rabbit ear hypertrophic scar model. The formulation was characterized for physicochemical, rheological, and film-forming properties, and its biocompatibility was assessed in accordance with ISO 10993 standards. Hypertrophic scars were induced by punch biopsy on rabbit ears (n = 6), followed by topical treatment with silicone gel alone or tranilast-loaded silicone gel for 40 days. Scar remodeling was evaluated using histological staining (H&E, Masson’s trichrome), α-SMA immunohistochemistry, and biochemical quantification of hydroxyproline and glycosaminoglycans. The gel rapidly polymerized on the skin to form a stable solid film and demonstrated favorable biocompatibility. Tranilast release reached approximately 81% within 24 h, following diffusion-controlled kinetics. Histological analyses revealed reduced epidermal and dermal thickness in treated groups compared to control, with the tranilast-loaded gel showing collagen fiber reorganization closely resembling healthy skin. Hydroxyproline content was significantly reduced in the tranilast group compared to both control and silicone-only groups (p < 0.01), accompanied by decreased α-SMA expression (27–30%), indicating suppression of myofibroblast activity. These findings demonstrate that the self-polymerizable silicone gel provides an effective delivery platform for tranilast, offering synergistic benefits in scar modulation and supporting its potential for advanced topical scar management.