Optimization of Palbociclib Nano Structured Lipid Carriers Loaded Transdermal Patch with Comprehensive ex vivo Skin Permeation and Retention Research for Management of Breast Cancer

Background: Palbociclib (PCB), a selective cyclin-dependent kinase 4/6 prescribe for hormone receptor-positive breast cancer, has low oral bioavailability and dose-limiting systemic toxicity. Objectives: In order to achieve prolonged drug administration and improved transdermal penetration, the current work sought to create and optimize a transdermal patch containing PCB based on Nanostructured Lipid Carriers (NLCs). Materials and Methods: After being adsorbed onto Neusilin® US2, PCB-NLCs were embedded to transdermal patches made using the solvent-casting method. The concentrations of HPMC K100 and Eudragit RS100 were optimized using a 2² complete factorial design, with tensile strength and time needed for 90% drug release chosen as the crucial quality criteria. Results: The honed formulation showed high drug content uniformity, skin-compatible pH, consistent thickness, and outstanding mechanical flexibility. PCB found to release steadily over a 72-hr period in vitro, according to Higuchi diffusion kinetics. Additionally, compared to the free drug solution, ex vivo permeation tests utilizing goat skin showed a 2.4-fold increase in steady-state flow and a considerably shorter lag time. Skin retention studies, indicating significant drug deposition into epidermal and dermal layers confirmed development of an intradermal drug depot. MTT assay and stability report ensures retaining of antitumor action of PCB in NLC form embed in transdermal patch. Conclusion: All things considered, the developed NLC-based transdermal patch is a promising alternative delivery system for PCB, providing enhanced skin penetration, controlled and sustained drug release, and the potential to reduce systemic toxicity linked to traditional oral therapy in the treatment of breast cancer.