Physcion-loaded, folic acid-conjugated DSPE-PEG liposomes for targeted therapy of ulcerative colitis.

Abstract

Conventional ulcerative colitis (UC) therapies suffer from limited efficacy and toxicity. Although physcion (PHY) has multi-target anti-inflammatory activity, its poor solubility and lack of targeting restrict clinical use. To overcome these issues, we developed folate receptor (FR)-targeted DSPE-PEG liposomes encapsulating PHY using thin-film hydration and central composite design optimization. The resulting liposomes showed uniform size (approximately 160 nm, PDI < 0.18), high entrapment efficiency (>92%), and good stability. In vitro release was significantly improved, and cellular uptake was enhanced in inflammatory EC cells via FR-mediated endocytosis. Pharmacokinetic studies revealed prolonged half-life and increased bioavailability, while tissue distribution confirmed colon-specific enrichment. In DSS-induced UC mice, targeted liposomes repaired colonic mucosa, reduced fibrosis, suppressed pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and alleviated oxidative stress through coordinated NF-κB/Nrf2 regulation, with efficacy superior to conventional liposomes and positive controls. Safety assessments showed no notable cytotoxicity to normal cells. This work offers a promising FR-targeted nanocarrier to overcome PHY's clinical limitations and provides a foundation for targeted UC therapy.

Key Findings

• Folate receptor-targeted DSPE-PEG liposomes encapsulating physcion were successfully developed with uniform size, high entrapment efficiency, and good stability.
• The targeted liposomes enhanced cellular uptake in inflammatory endothelial cells via folate receptor-mediated endocytosis and showed colon-specific enrichment in vivo.
• In DSS-induced ulcerative colitis mice, the targeted liposomes repaired colonic mucosa, reduced fibrosis, suppressed pro-inflammatory cytokines, and alleviated oxidative stress through coordinated NF-κB/Nrf2 regulation.

Clinical Significance

Citation

Guan Zhenhua, Xu Yi, Liang Xuyanget al.. Physcion-loaded, folic acid-conjugated DSPE-PEG liposomes for targeted therapy of ulcerative colitis. Journal of drug targeting. 2026-Jun-28.