Liposomal Delivery Systems for Berberine: Formulation Strategies, Pharmacokinetic Enhancement, and Therapeutic Applications

Abstract:Berberine (BBR) is a plant-derived isoquinoline alkaloid with a remarkably broadpharmacological profile spanning antidiabetic, hypolipidemic, antitumor, antimicrobial, antiviral,and anti-inflammatory activities. Despite this therapeutic promise, its clinical utility is severelyconstrained by an absolute oral bioavailability of well below 1%, arising from poor aqueoussolubility, self-aggregation under gastric pH, extensive P-glycoprotein-mediated intestinal efflux,and substantial hepato-intestinal first-pass metabolism. Liposomal encapsulation has emerged asone of the most extensively investigated nanocarrier strategies to overcome these limitations,exploiting the amphipathic phospholipid bilayer to improve solubilization, protect the alkaloidfrom enzymatic and efflux-mediated loss, and enable surface functionalization for site-specificdelivery. This review synthesizes the physicochemical rationale for berberine's poorbioavailability, the principal methods used to fabricate and characterize berberine-loadedliposomes (thin-film hydration, proliposome/solid-template technology, reverse-phaseevaporation, and high-pressure homogenization/microfluidics), and the comparativepharmacokinetic and pharmacodynamic outcomes reported across oral hyperlipidemia models,oncology applications (including mitochondria-targeted and photodynamic therapy platforms),and inflammatory bowel disease models. Representative preclinical and early clinical studies aretabulated to allow direct comparison of vesicle size, entrapment efficiency, and therapeuticoutcome. The review further situates liposomal berberine within the broader landscape ofclinically approved liposomal nanomedicines (e.g., Doxil®) to evaluate translational feasibility,and concludes by identifying unresolved challenges in scale-up, long-term stability, andregulatory characterization that must be addressed before liposomal berberine can progress frombench to bedside.