Control of Skin Carcinoma via Sonidegib-loaded Transbilosomes

The uncontrolled proliferation of abnormal skin cells is the hallmark of skin carcinoma. Sonidegib (SDB), a potent Hedgehog pathway inhibitor, is clinically approved for the treatment of skin carcinoma. However, its therapeutic utility is restricted by poor bioavailability, high hydrophobicity, and significant systemic adverse effects. This study aimed to develop an intratumor SDB-loaded transbilosomes (SLT) formulation to improve localized therapeutic efficacy and mitigate systemic toxicity. Several SLT formulations were developed and optimized using Design-Expert® software. The optimized SLT formulation was evaluated for safety, intratumor retention, and efficacy using a DMBA-induced skin carcinoma rat model. Results demonstrated that the optimal SLT formulation achieved a 68.87% reduction in drug release after 24 hours compared to free SDB. Pharmacokinetic evaluation revealed a 7.78-fold increase in relative systemic bioavailability compared to oral SDB. In vivo efficacy studies showed an 84.22% reduction in tumor volume in the intratumor SLT-treated group, with no observed fatalities compared to the oral SDB. Histopathological and safety assessments confirmed the significant antiproliferative effects and the favorable preliminary safety profile of the intratumor SLT formulation. These findings suggest that the intratumor SLT formulation provides an effective option for the management of skin carcinoma.