A natural deep eutectic solvent formulation promotes hair growth by enhancing the transdermal delivery and bioactivity of hydroxytyrosol

Abstract

Hair loss is a widespread condition with androgenetic alopecia (AGA) representing the most prevalent subtype. The excessive accumulation of reactive oxygen species (ROS) in the perifollicular microenvironment and subsequent dysregulation of the follicular milieu is recognized as a major driver underlying the pathogenesis of AGA. Hydroxytyrosol (HT), a natural polyphenolic compound with potent antioxidant activity, has demonstrated protective effects against oxidative stress-induced inflammation in dermal cells. However, the clinical application of HT is limited by its high hydrophilicity, which restricts penetration across the skin lipid barrier and results in poor cutaneous absorption. Additionally, HT is prone to oxidation, further compromising its efficacy. To overcome these challenges, we developed a pro-permeable deep eutectic solvent (DES)-based system, composed of betaine, urea, and lactic (BUL), to facilitate the transdermal delivery of HT while preserving bioactivity. The BUL-based delivery system enabled cutaneous penetration to a depth of at least 180 µm, achieving over threefold greater permeation than aqueous solutions. In vivo studies confirmed that HT@BUL effectively promoted hair regrowth and exhibited high biocompatibility, whereas results of in vitro assays demonstrated that HT-loaded BUL exhibited intrinsic ROS-scavenging activity, ability to stimulate proliferation, and capacity to mitigate cellular senescence. Our research highlights the therapeutic potential of combining antioxidant molecules with BUL for the promotion of hair regrowth.