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

Abstract:
Berberine (BBR) is a plant-derived isoquinoline alkaloid with a remarkably broad
pharmacological profile spanning antidiabetic, hypolipidemic, antitumor, antimicrobial, antiviral,
and anti-inflammatory activities. Despite this therapeutic promise, its clinical utility is severely
constrained by an absolute oral bioavailability of well below 1%, arising from poor aqueous
solubility, self-aggregation under gastric pH, extensive P-glycoprotein-mediated intestinal efflux,
and substantial hepato-intestinal first-pass metabolism. Liposomal encapsulation has emerged as
one of the most extensively investigated nanocarrier strategies to overcome these limitations,
exploiting the amphipathic phospholipid bilayer to improve solubilization, protect the alkaloid
from enzymatic and efflux-mediated loss, and enable surface functionalization for site-specific
delivery. This review synthesizes the physicochemical rationale for berberine's poor
bioavailability, the principal methods used to fabricate and characterize berberine-loaded
liposomes (thin-film hydration, proliposome/solid-template technology, reverse-phase
evaporation, and high-pressure homogenization/microfluidics), and the comparative
pharmacokinetic 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 are
tabulated to allow direct comparison of vesicle size, entrapment efficiency, and therapeutic
outcome. The review further situates liposomal berberine within the broader landscape of
clinically approved liposomal nanomedicines (e.g., Doxil®) to evaluate translational feasibility,
and concludes by identifying unresolved challenges in scale-up, long-term stability, and
regulatory characterization that must be addressed before liposomal berberine can progress from
bench to bedside.