Novel Nano-delivery Systems for Berberine and Epigallocatechin Gallate: Enhancing Bioavailability and Anti-obesity Therapeutic Efficacy

Abstract

Obesity affects hundreds of millions of adults worldwide and represents a major risk factor for metabolic disorders, including type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease. Berberine (BBR) and epigallocatechin gallate (EGCG) are bioactive phytochemicals that exhibit anti-obesity effects through multiple mechanisms, including activation of AMP-activated protein kinase (AMPK), inhibition of lipogenesis, stimulation of thermogenesis, and modulation of the gut microbiota. However, their therapeutic applications are limited by poor oral bioavailability due to low aqueous solubility, chemical instability, and extensive first-pass metabolism, which restrict their absorption and biological efficacy. A comprehensive literature analysis was conducted on novel nanocarrier platforms, including lipid-based systems (liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions), polymeric nanoparticles (PLGA, chitosan, protein-based carriers), inorganic nanocarriers, and molecular complexation strategies for BBR and EGCG delivery in obesity models. Recent studies indicate that nano-formulation strategies can substantially enhance the solubility, stability, absorption, and bioavailability of BBR and EGCG compared with conventional formulations. Different nanocarrier systems demonstrate distinct advantages; however, limitations related to formulation stability, scalability, safety assessment, reproducibility, and regulatory approval remain major barriers to clinical application. Preclinical studies suggest that nano-delivered BBR and EGCG may improve metabolic outcomes, including reductions in body weight gain, adiposity, inflammation, and hepatic lipid accumulation, although further validation in well-designed clinical studies is required. This review systematically evaluates advanced nano-delivery systems designed to overcome bioavailability barriers of BBR and EGCG, focusing on pharmacokinetic enhancement, targeted delivery, and improved anti-obesity efficacy across preclinical models to inform clinical translation strategies. Nanomedicine-based delivery platforms represent a promising strategy to unlock the anti-obesity therapeutic potential of BBR and EGCG. Future research should focus on the co-delivery of Nanoformulations that utilise the complementary anti-obesity effects of BBR and EGCG and evaluate their clinical feasibility.