Physcion-Loaded, Folic Acid-Conjugated DSPE-PEG Liposomes for Targeted Therapy of Ulcerative Colitis

Conventional therapeutic agents for ulcerative colitis (UC) exhibit limited efficacy and toxic side effects. Although the natural compound physcion (PHY) demonstrates multi-target anti-inflammatory potential, its clinical application is constrained by poor water solubility and insufficient targeting capability. To address this, we developed folate receptor (FR)-targeted DSPE-PEG liposomes to encapsulate PHY and enhance colonic delivery efficiency. The formulation was prepared using the thin-film hydration method and optimised by central composite design. The resulting liposomes exhibited uniform particle size (PS) (approximately 160 nm, polydispersity index [PDI] < 0.18), high entrapment efficiency (EE, >92%), and excellent stability under storage conditions. In vitro release experiments revealed that the targeted liposomes significantly improved PHY release efficiency. Cellular uptake studies demonstrated enhanced uptake of the FA-modified liposomes in inflammatory EC cells, with the findings being consistent with FR-associated uptake. Pharmacokinetic studies demonstrated that liposomal formulation markedly prolonged the drug half-life and enhanced bioavailability. Tissue distribution experiments further validated its colon-specific enrichment capacity. In a dextran sulfate sodium (DSS)-induced UC mouse model, the targeted liposomes significantly repaired colonic mucosal structure and reduced fibrotic deposition. The treatment inhibited release of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and alleviated oxidative stress, which is consistent with coordinated regulation of NF-κB/Nrf2-associated inflammatory and antioxidant responses. The therapeutic efficacy surpassed that of conventional liposomes and positive control drugs. Safety assessments indicated no significant cytotoxicity toward normal cells. This study provides an effective targeted drug delivery system to overcome limited clinical applications of PHY and establishes a theoretical and technological foundation for FR-targeted delivery strategies in UC.