Thermosensitive polygalacturonic acid glycoprotein hydrogel encapsulating bionic shikonin nanoparticles for the treatment of psoriasis

Abstract

Psoriasis is histopathologically characterized by hyperproliferation of keratinocytes, loss of the granular layer, and elongation and thickening of the rete ridges in the epidermis. The thickening of the stratum corneum in psoriatic skin poses a significant barrier to effective drug delivery, as many therapeutic agents with poor solubility, limited release, and side effects struggle to penetrate the skin and achieve prolonged retention, thereby limiting their therapeutic efficacy. To address these challenges, we developed a non-invasive transdermal delivery system. In this system, biomimetic shikonin nanoparticles (CNC) were modified with citric acid and combined with a deep eutectic solvent (DES) composed of L-lysine (L-Lys) and citric acid (CA), forming a CCNCD complex that significantly enhanced the transdermal permeability of CNC. The CCNCD complex was then loaded into a thermosensitive composite hydrogel composed of polygalacturonic acid (PGA)-grafted bovine serum albumin (BSA) and the thermosensitive material F-127 (FPB-CCNCD). This hydrogel exhibited sol-gel transition at body temperature, enabling uniform application on psoriatic skin and prolonging the retention time of CCNCD. The FPB-CCNCD system demonstrated high drug loading capacity, uniform particle size distribution, sustained release, excellent adhesion, enhanced skin retention and penetration in psoriatic-like lesions, and effective targeting of keratinocytes. In vitro experiments revealed that CCNC exhibited strong targeting ability, promoted keratinocyte apoptosis, and reduced the expression of inflammatory cytokines (TNF-α, IL-1β, and IL-6). In an imiquimod-induced psoriatic mouse model, FPB-CCNCD significantly alleviated psoriatic symptoms and reduced the expression of inflammatory factors. Therefore, FPB-CCNCD holds great promise for providing new clinical treatment strategies for psoriasis.