Virus Mimicking Liposomes Incorporated Microneedles Delivery Platform for Efficient Skin Penetration and Enhanced Cellular Uptake

Abstract

Transdermal delivery is an attractive route for the treatment of skin disease. However, its therapeutic effectiveness is significantly hampered by the stratum corneum and cell membrane barriers. Herein, we reported a novel liposomes incorporated microneedles (MNs) delivery platform to address these two key challenges. Conventional liposomes were surface modified with membrane-anchoring fusogenic proteins mimicking pH-responsive, comb-like pseudopeptides containing relatively long alkyl side chains. The liposomes-containing MNs were fabricated with biodegradable and biocompatible silk fibroin with sufficient mechanical strength using micromolding technology. The degradation and release profile of liposomes from the MNs delivery platform can be manipulated by controlling the liposomes to silk fibroin ratio, and the released liposomes well-maintained their original spherical shape and pH-responsive functionality. Remarkably enhanced in vitro skin permeation was observed in the polymer modified liposomes incorporating MNs delivery platform compared to the ones without MNs facilitation. Enhanced cellular uptake and potency against cancer cells of the pH-responsive, comb-like pseudopeptides modified liposomes incorporating MNs delivery platform were demonstrated. These results suggest its potential applications for efficient skin penetration and enhanced cellular uptake, which is of crucial importance for skin disease treatment.