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Novel amphiphilic lipid augments the co-delivery of erlotinib and IL36 siRNA into the skin for psoriasis treatment. | LitMetric
In this study, we demonstrate for the first time the concurrent transdermal delivery of erlotinib and IL36α siRNA as a potential dual therapy for psoriasis. The objectives were to develop and evaluate lipid nanocarriers (CYnLIP) using a novel pyrrolidinium lipid to disrupt the skin barrier for enhanced transdermal delivery. CYnLIP (132.00±6.23nm) had encapsulation efficiency of 49.04±2.54% for erlotinib. DSC confirmed encapsulation of erlotinib within CYnLIP. Atomic Force Microscopy demonstrated notable topographical changes in the stratum corneum of skin permeated with CYnLIP that were absent in skin hydrated with water. Peak force distance curves also exhibited a more permeable membrane for CYnLIP-incubated skin than hydrated skin. Permeation studies showed enhanced (p<0.01) skin retention of erlotinib by CYnLIP (40.76-fold) than solution and more pronounced fluorescence at deeper layers of the skin for fluorescein-labeled siRNA-CYnLIP than solution. The enhanced co-transdermal delivery of erlotinib and IL36α siRNA by CYnLIP efficaciously treated psoriatic-like plaques in C57BL/6 mice (PASI score of 1) compared to imiquimod-only treatment (PASI score of 4). IHC and western blotting revealed reduction in epidermal hyperplasia (Ki67) and in the dermal infiltration of inflammatory cytokines (IL36α, pSTAT3, TNFα, NFκB, IL23 and IL17) for erlotinib/IL36α siRNA-CYnLIP (p<0.05) comparable to Tacrolimus but markedly less than imiquimod-only treatment.
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