QBD Driven Approach Design and Optimization of Lipid-Based Nanoformulation of Cannabidiol for Enhanced Treatment of Non-Melanoma Skin Cancer

Introduction: The non-melanoma skin cancer (NMSC) is a very commonly detected malignancy globally, contributing significantly to patient morbidity and placing a substantial burden on healthcare systems. Objective: This study aims to develop a stable cannabidiol (CBD)-incorporated nanostructured lipid carrier (NLC) for treating the non-melanoma skin cancer. Methods: In the current study, we report the design, development and characterization of a cannabidiol (CBD)-incorporated nanostructured lipid carrier (NLC) gel formulation (CBD loaded NLC gel), a novel topical therapeutic approach for treating the NMSC. The optimization of the NLC was effectively carried out using a central composite design (CCD), which enabled the systematic evaluation of formulation variables and their impact on key physicochemical parameters. Results: The final optimized CBD-NLC formulation exhibited mean particle size of 154.7 nm and a zeta potential of +30.12 mV, indicating good stability and potential for effective skin interaction. The cumulative drug release and skin permeation studies using Wistar rat skin demonstrated enhanced and sustained delivery of CBD into the epidermal and dermal layers, facilitated by the lipid-based nanocarrier system. Further, the cytotoxic ability of the CBD Loaded NLC formulation was evaluated using A375 human melanoma cells. The MTT assay revealed a significantly lower IC₅₀ value of 3.07 µg/mL for the CBD loaded NLC gel compared to conventional formulations, indicating improved anticancer activity. Conclusion: Cannabidiol (CBD)-incorporated nanostructured lipid carrier (NLC) gel formulation exhibited suitable release, skin permeation and cytotoxic potential for the treatment the non-melanoma skin cancer.