Abstract: 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. The infographic is arranged in three connected sections from left to right. The first section illustrates the challenge of gentiopicroside administration, featuring a container labeled “Gentiopicroside” with callouts indicating “Low oral bioavailability” . The middle section depicts “Nanodelivery Strategies” with illustrations of specific carrier systems, including PLGA nanospheres, PC-SNEDDS, chitosan nanoparticles, ZIF-8 frameworks, and electrospun nanofibers, all linked to the outcome “High bioavailability”. A directional arrow labeled “Regulation” connects to the third section. The right section summarizes the therapeutic effects on inflammation-associated skin lesions, highlighting modulation of “Inflammation”, “ROS”, “Neovascularization”, and “Antibacterial”, centered around a cross-sectional illustration of the skin labeled “PsO & DFU”.Infographic on nanodelivery strategies of GPS for enhanced bioavailability and therapeutic regulation in PsO and DFU. Keywords: gentiopicroside, nanodelivery, psoriasis, diabetic foot ulcers, chitosan, skin lesions
Wang et al. (Wed,) studied this question.