Artificial intelligence-driven hydrogel microneedle patches integrating 5-fluorouracil inclusion complex-loaded flexible pegylated liposomes for enhanced non-melanoma skin cancer treatment

The current study focused on the development of crosslinked hydrogel microneedle patches (cHMNs) incorporating 5-FU-hydroxypropyl beta-cyclodextrin inclusion complex-loaded flexible PEGylated liposomes (5-FU-HPβCD-loaded FP-LPs) to enhance treatment efficacy and reduce drug toxicity. The research utilized artificial intelligence (AI) algorithms to design, optimize, and evaluate the cHMNs. Various AI models were assessed for accuracy, with metrics such as root mean square error and coefficient of determination guiding the selection of the most effective formulation. The physicochemical and mechanical properties, swelling behavior, in vitro skin permeation, and safety of the chosen cHMNs were tested. The results demonstrated that the 5-FU-HPβCD-loaded FP-LPs, stabilized with limonene, had an optimal particle size of 36.23 ± 2.42 nm, narrow size distribution, and zeta potential of –10.24 ± 0.37 mV, with high encapsulation efficiency. The cHMNs exhibited a conical needle shape with sufficient mechanical strength to penetrate the stratum corneum up to approximately 467.87 ± 65.12 μm. The system provided a high skin permeation rate of 41.78 ± 4.26 % and significant drug accumulation in the skin. Additionally, the formulation was proven safe in cell culture while effectively inhibiting cancer growth and promoting apoptosis. This study highlights the potential of AI-enhanced cHMNs for delivering 5-FU-HPβCD-loaded FP-LPs transdermally, offering a promising new treatment avenue for non-melanoma skin cancers.