Nanodelivery of Gentiopicroside for Inflammatory Skin Lesions: Insights from Psoriasis and Diabetic Foot Ulcers.

Inflammation-associated skin lesions, including psoriasis (PsO) and diabetic foot ulcers (DFU), greatly impair patients' quality of life. Gentiopicroside (GPS), a key iridoid glycoside from Gentiana species, exhibits anti-inflammatory, antioxidant, and wound-healing properties, but its clinical application is limited by low oral bioavailability and poor skin permeability. Nanodelivery strategies have been actively explored to overcome these limitations. The objective of this review was to critically analyze recent breakthroughs in GPS-loaded nanodelivery approaches for the treatment of inflammation-associated skin lesions, especially PsO and DFU, including the impact of these approaches on GPS bioavailability, efficacy, and safety profile. Oral bioavailability of GPS can be improved by poly (lactic-co-glycolic acid) (PLGA) nanospheres and phospholipid-complex self-nanoemulsifying drug delivery systems (PC-SNEDDS), while skin-targeted delivery and sustained release can be enhanced by chitosan (CHI) nanoparticles, electrospun nanofibers, ZIF-8 metal-organic frameworks, and nanoscale hydrogels. These nanodelivery technologies improve the translational potential of GPS for chronic inflammatory skin diseases. Although GPS-loaded systems have not yet entered clinical trials, analogous nanotechnologies have demonstrated enhanced drug stability, bioavailability, safety, and patient tolerability in treatments of other skin diseases, highlighting their strong potential for clinical translation. Future efforts toward clinical translation may focus on establishing common evaluation criteria, conducting full-scale toxicological and biodistribution tests, and implementing Good Manufacturing Practice (GMP)-scale-up projects with multicenter preclinical trials.