Hyaluronic acid modified liposomes with enhanced transdermal delivery of methotrexate for psoriasis treatment

Psoriasis is a chronic inflammatory skin disorder characterized by immune dysregulation and cutaneous symptoms. Methotrexate (MTX), efficacious in psoriasis, suffers from limited transdermal permeability due to its hydrophilic nature. Liposomal nanomedicine, which offers increased bioavailability and targeted delivery with minimized systemic effects, is a promising approach. The application of hyaluronic acid (HA) as a penetration enhancer and modifier leverages its binding to the upregulated CD44 receptor in psoriasis, enhancing the efficacy of liposomes. In this study, we synthesized HA-modified liposomes by conjugating HA with distearoyl phosphatidyl ethanolamine-poly (ethylene glycol) (DSPE-PEG) and encapsulated methotrexate for targeted treatment of psoriasis. The research entailed the meticulous preparation and physicochemical characterization of these HA-modified liposomes, followed by in vitro transdermal delivery assays, cellular uptake studies, and the development of a psoriasis animal model to rigorously assess therapeutic efficacy. Our findings underscore the significant improvement in methotrexate's transdermal penetration and retention within psoriatic lesions afforded by the HA-modified liposomes, indicating a novel and efficacious therapeutic approach for the management of dermatological disorders.