Exploring roflumilast transferosomes in pluronic-hyaluronic acid hydrogel through comprehensive in-vitro and in-vivo evaluation

Roflumilast (RF) is a phosphodiesterase-4 inhibitor that has been recently approved to treat psoriasis. This study aims to enhance the topical anti-psoriasis pharmacological effect of RF through the preparation of RF-loaded transferosomes (TRFs) and loading them in a poloxamer-hyaluronic acid hydrogel. TRF were prepared through the ethanol injection technique in which different ratios of lipid: surfactant was examined to determine the optimum formula. F4 and F12 with two different drug concentrations (0.1 % and 0.2 %) were found to be the most optimized formulations according to the in-vitro characterizations. These formulations had the highest percentage of drug release after 24 h (102.74 % and 106.95 %, respectively), high EE % (81.9 % and 91.2 %, respectively), and small vesicle size (101.4 nm and 218.5 nm, respectively). F4 and F12 were then incorporated into poloxamer-hyaluronic acid hydrogel followed by further in-vivo examination. In vivo pharmacological study assessed the possible positive impact of RF-TRF Hydrogel in treating psoriasis by utilizing an Imiquimod (IMQ)-induced psoriasis-like mouse model. Psoriasis Area Severity Index (PASI) was employed to assess the inflammation severity on the backs of mice concerning erythema, thickness, and scaling scoring. Histopathological examination to evaluate epidermal thickness and immunohistochemical analysis to determine proliferating cell nuclear antigen (PCNA) expression in mice's lesional skin also were employed. Our findings indicated that RF-TRF hydrogel effectively decreased the PASI scores. Histopathological examination showed a significant decrease in epidermal thickness. Additionally, RF-TRF hydrogel successfully reduced the expression of PCNA in the skin lesions caused by IMQ in mice. In conclusion, our work showed that RF-TRF hydrogel showed significant enhancement of the anti-psoriasis effect.