Psoriasis is a chronic inflammatory skin disease characterized by disruption of the stratum corneum lipid organization, which significantly limits the effectiveness of topical therapies. Although methotrexate (MTX) is widely used for moderate-to-severe psoriasis, its systemic administration is associated with adverse effects, whereas topical delivery remains inefficient due to the skin barrier. In this context, this work proposes a biomimetic strategy combining interfacial lipid models and microneedle (MN)-based systems to improve localized MTX delivery. Langmuir monolayers composed of phosphatidylcholine (PC), cholesterol (Chol), and ceramide NS (Cer NS) were employed as simplified models of the skin barrier to investigate lipid organization and drug-lipid interactions. Surface pressure-area isotherms, compressibility modulus, and surface potential analyses revealed strong composition-dependent behavior, with the PC:Chol:Cer NS (4:1:1) system showing the most balanced interfacial properties, including favorable packing, stability, and mechanical response. Interaction with MTX induced monolayer expansion and altered dipolar organization, indicating drug incorporation and disruption of lipid packing in a composition-dependent manner. The optimized lipid systems were transferred onto polycaprolactone (PCL) MNs using Langmuir-Blodgett and Langmuir-Schaefer techniques. Atomic force microscopy (AFM) and infrared nanospectroscopy (NanoIR) confirmed the formation of continuous lipid coatings and the presence of MTX, while revealing composition-dependent morphological and chemical heterogeneity. Mechanical compression assays demonstrated that lipid functionalization enhanced MN stiffness, particularly in ceramide-containing systems, which is advantageous for skin insertion. Preliminary drug release studies performed by UV-Vis spectroscopy confirmed MTX release, and a calibration curve enabled quantitative analysis. However, the relatively low loading efficiency (~10-20%) highlights drug-lipid affinity as a key limiting factor.
Acknowledgments: The authors gratefully acknowledge the financial support provided by FAPESP, CNPq, CEPID-CEMol, and INCTBio-LK.
Comissão Organizadora
Pedro Alves da Silva Autreto
Comissão Científica
Ferramenta completa de submissão, avaliação e publicação de anais para eventos científicos.
