Regulating Size and Charge of Liposomes in Microneedles to Enhance Intracellular Drug Delivery Efficiency in Skin for Psoriasis Therapy

Abstract The stratum corneum (SC) and cell membrane are two major barriers that hinder the therapeutic outcomes of transdermal drug delivery for the treatment of skin diseases. While microneedles (MNs) can efficiently penetrate the SC to deliver nanomedicines, the optimization of physicochemical properties of nanomedicines in MNs to enhance their in vivo cellular delivery efficiency remains unclear. Here, how the size and surface charge of drug‐loaded liposomes in MNs influence the retention time and cellular delivery in psoriatic skin is systematically investigated. The results indicate that while 100 nm negatively‐charged liposomes in MNs show higher cellular uptake in vitro, 250 and 450 nm liposomes could enhance skin retention and the long‐term in vivo cellular delivery efficiency of drugs. Moreover, 250 nm cationic liposomes with a stronger positive charge show an extraordinarily long skin retention time of 132 h and significantly higher in vivo cellular internalization. In the treatment study, dexamethasone (dex)‐loaded cationic liposomes‐integrated MNs show better therapeutic outcomes than dex‐loaded anionic liposomes‐integrated MNs in a psoriasis‐like animal model. The design principles of liposomes in MN drug delivery systems explored in the study hold the potential for enhancing the therapeutic outcomes of psoriasis and are instrumental for successful translation.