Transdermal Delivery of 5-Aminolevulinic Acid by Nanoethosome Gels for Photodynamic Therapy of Hypertrophic Scars.

5-Aminolevulinic acid (ALA)-loaded nanoethosome (ALA-ES) gels are successfully prepared to realize a transdermal delivery of ALA, and they provide a feasible approach for the photodynamic therapy (PDT) of hypertrophic scars (HS). Herein, the morphological and physicochemical features indicate that ALA-ES is stable in gel matrix. In vitro transdermal penetration studies suggest ALA-ES gels can overcome the compact dermal barrier and deliver more ALA into human HS tissue. In vivo delivery studies further reveal that ALA-ES gels can penetrate into rabbit HS tissue to facilitate ALA accumulating in hypertrophic scar fibroblast (HSF) and converting into protoporphyrin IX in the cytoplasm. Utilizing transmission electron microscopy, the visual in vivo penetration process indicates ALA-ES penetrate into HS tissue utilizing its deformable membrane, enters HSF by a pinocytotic-like mechanism, and then releases ALA in the cytoplasm. Subsequently, PDT efficacy is assessed using rabbit HS models. The morphological and histological analysis reveal that ALA-ES gels can improve HS by promoting HSF apoptosis, remodelling collagen fibers and increasing MMP3 expression. The results demonstrate that ALA-ES gels are suitable in clinical treatment of HS and make a substantial progress within the field.