Gunduz Tavlar, NerminBalcioglu, SevgiErenler, Ayse SebnemAtes, Burhan2025-10-242025-10-2420252637-6105https://doi.org/10.1021/acsapm.5c01134https://hdl.handle.net/20.500.12899/3511Breast cancer remains the most prevalent cancer worldwide and a leading cause of mortality in women, demanding advanced drug delivery strategies. Ribociclib, a CDK4/6 inhibitor used in hormone-dependent breast cancer therapy, is effective but requires high oral doses, leading to severe systemic toxicity. To overcome this limitation, we developed electrospun PCL/CS-based transdermal patches designed to enhance drug bioavailability, prolong half-life, and minimize side effects. Extensive characterization confirmed the structural integrity and performance of the patches, demonstrating high swelling capacity (81-93%), superior thickness uniformity (95-100%), and exceptional folding endurance (1000-1540 cycles). The patches exhibited excellent weight homogeneity (92-99%) for consistent drug distribution, while adhesion strength (144-386 kPa) ensured stable skin attachment. HPLC analysis revealed sustained Ribociclib release (similar to 95% over 48 h), and ex vivo rat skin diffusion studies confirmed high permeability (68-81%), indicating effective transdermal absorption. Drug retention efficiency exceeded 95% in both the reservoir and drug release layers. Biocompatibility assessments with L-929 fibroblasts demonstrated excellent cell viability (90-95%), while MCF-7 breast cancer cells exhibited potent cytotoxicity (93-94%), comparable to standard Ribociclib treatment. Despite the therapeutic potential of transdermal drug delivery systems (TDDS), Ribociclib has been scarcely explored in this context. This study pioneers a promising alternative for controlled, sustained drug release, potentially revolutionizing breast cancer treatment by improving patient compliance, reducing systemic toxicity, and enhancing therapeutic outcomes.eninfo:eu-repo/semantics/closedAccessbreast cancer; transdermal patch; Ribociclib; electrospinning; biocompatibilityArticle10.1021/acsapm.5c0113471596699680WOS:001532268000001N/A