Synergistic Transdermal Delivery of Nanoethosome Embedding in Hyaluronic Acid Nanogels for Enhancing Photodynamic Therapy
Photodynamic therapy (PDT) is new therapeutic strategy for hypertrophic scar (HS), but it is limited by low drug utilization. Transdermal delivery based on nanoethosome (ES) has attracted considerable attention as potential clinical strategy in PDT treating HS. However, free ES is unsatisfactory by its instability and non-targeting, which causes non-effective delivery and low drug utilization. Herein, 5-Aminolevulinic acid (ALA)-loaded ES (ES-ALA) embedding in hyaluronic acid (HA) meshes (HA/ES-ALA), a novel synergistic transdermal delivery nanogels, is developed for enhancing PDT of HS. HA/ES-ALA has the unique structure and property to protect unilaminar ES-ALA with HA meshes and actively target to hypertrophic scar fibroblasts (HSF) with HA receptors. Both in vitro and in vivo experiments demonstrate that HA/ES-ALA has remarkable transdermal delivery ability with penetrating channels and membrane-fusion mechanism. Meanwhile, the synergistic delivery mechanism is visually characterized as three stages: synergistic penetration, targeting aggregation and transmembrane delivery. With synergistic effect, HA/ES-ALA can realize a targeted transdermal delivery, and significantly improve ALA utilization and enhance PDT efficacy. The results demonstrate the effective transdermal delivery route to enhance therapy for HS as well as other skin diseases.