Sorafenib Loaded Nanoemulsion for Improved Oral Delivery and Therapeutic Efficacy in Hepatocellular Carcinoma

Background: Sorafenib is a clinically approved multikinase inhibitor for hepatocellular carcinoma (HCC); however, its oral bioavailability is limited due to poor solubility and extensive first-pass metabolism. Nanoemulsion-based delivery offers a promising strategy to enhance solubility, drug retention, and therapeutic efficacy. Objective: The present study aimed to develop and optimize Sorafenib-loaded nanoemulsions for improved oral delivery and sustained release in HCC therapy. Methods: Sorafenib nanoemulsions were prepared using spontaneous emulsification with Capryol® 90 as oil, Tween® 80 as surfactant, and Transcutol® P as co-surfactant. Formulation variables (oil, surfactant, and co-surfactant concentrations) were optimized using a Design of Experiments (DoE) approach to achieve maximum encapsulation efficiency, controlled particle size, and sustained drug release. Characterization included particle size analysis, encapsulation efficiency, and in vitro drug release studies. Results: The optimized nanoemulsion (F-16) contained 15% Capryol® 90, 20% Tween® 80, and 9.372% Transcutol® P, with predicted responses of 92.85% encapsulation efficiency, 183.92 µm particle size, and 78.70% cumulative drug release. Experimental evaluation closely matched predictions, with values of 91.85 ± 0.4%, 180.75 ± 1.5 µm, and 76.25 ± 0.6%, respectively, demonstrating excellent model reliability. Comparative analysis with marketed Sorafenib capsules (Nexavar®) revealed superior encapsulation, smaller particle size, and enhanced drug release for the nanoemulsion, indicating improved oral delivery potential. Conclusion: The study successfully demonstrates that Sorafenib-loaded nanoemulsions offer a robust and optimized platform for oral delivery, with enhanced solubility, controlled release, and potential for improved therapeutic efficacy in hepatocellular carcinoma treatment