Nano-liposomal curcumin–berberine hybrid formulation for targeted modulation of pancreatic inflammation and oxidative stress in pancreatitis

Title : Nano-liposomal curcumin–berberine hybrid formulation for targeted modulation of pancreatic inflammation and oxidative stress in pancreatitis

Abstract:

Pancreatitis is a complex inflammatory disorder of the pancreas marked by excessive oxidative stress, dysregulated cytokine signaling, and pancreatic enzyme leakage, leading to progressive tissue damage. Current therapeutic strategies are largely supportive and lack site-specific delivery, limiting effective and sustained modulation of pancreatic inflammation. The present study aimed to design, develop, and evaluate a nano-liposomal Curcumin–Berberine hybrid formulation for targeted management of pancreatic inflammation and oxidative stress.

Curcumin and Berberine were co-encapsulated into phosphatidylcholine-based liposomes, stabilized with cholesterol and surface-functionalized with N-Acetylcysteine (NAC) to enhance pancreatic affinity, redox responsiveness, and antioxidant capacity. Preformulation studies established complementary physicochemical properties of the phytoconstituents, confirming their suitability for co-encapsulation. FTIR and DSC analyses demonstrated drug–excipient compatibility and molecular dispersion within the lipid bilayer, while accelerated stability studies confirmed formulation robustness.

Nano-liposomes were prepared using the thin film hydration method followed by probe sonication, yielding uniform nanosized vesicles. In vitro evaluations revealed enhanced antioxidant activity (IC₅₀=12.3 µg/mL), controlled zero-order drug release kinetics (t_1/2=8.6 h), and significantly improved cellular uptake in AR42J pancreatic acinar cells. The synergistic Curcumin–Berberine combination effectively suppressed NF-κB-mediated pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), reduced reactive oxygen species generation, and supported restoration of pancreatic enzyme homeostasis.

Overall, the NAC-functionalized nano-liposomal Curcumin–Berberine system offers a stable, biocompatible, and targeted therapeutic platform with the potential to improve localized pancreatic delivery, minimize systemic toxicity, and provide effective management of both acute and chronic pancreatitis. This formulation warrants further in vivo and translational investigation.