Retinoid-loaded ionic liquid nanoparticles: Decreased irritation, enhanced transdermal delivery and synergistic anti-wrinkle

Although retinol and its derivatives are effective anti-aging substances, they can induce “retinoid dermatitis.” To solve this problem, a novel 4-t-butylcyclohexanol α-lipoic acid ionic liquid (BLA-IL) was prepared and confirmed. Retinol can be directly dissolved into BLA-IL, encapsulated into nanoparticles (NPs) and form retinoid-loaded ionic liquid NPs. In-vivo and ex-vivo studies investigated the developed formulation's safety, transdermal enhancement, and efficacy. Safety assessments revealed that BLA-IL-mediated TRPV1 antagonism was achieved. In particular, IL-NPs increase the amount of retinoid in the skin by 4.3 times compared to the free retinoid and 27 % more than NPs. Based on in vivo and in vitro experiments, BLA-IL synergistically doubled the effect of fibroblast COL-I synthesis, with upregulation to 756.9 %, simultaneously enhancing COL-I, COL3A1, and Elna gene expression and inhibiting MMP-1, reactive oxygen species, and neutrophil aggregation. Clinically, retinoid-loaded IL-NPs significantly improved wrinkles, R2, collagen intensity, ITA°, and l -value compared to free retinoid in volunteers. In conclusion, this study displayed that BLA-IL NPs could promote transdermal delivery and achieve synergistic anti-aging efficacy. It could be a promising technology combining IL and nano-technology in the pharmaceutic and cosmetic transdermal areas.