Nanotechnology-driven delivery platforms overcoming the bioavailability challenges of berberine

Berberine (BBR) is a bioactive natural alkaloid with broad pharmacological activities, including metabolic regulation, anti-inflammatory effects, and cardiovascular protection. However, its clinical translation is severely limited by poor aqueous solubility, low oral bioavailability, rapid metabolism, P-glycoprotein-mediated efflux, first-pass metabolism, and rapid systemic clearance. In recent years, nanotechnology-driven delivery systems have emerged as promising strategies to overcome these pharmacokinetic barriers. This review provides a concise overview of recent advances in nanoplatforms designed to enhance the bioavailability and therapeutic efficacy of berberine. We summarize representative delivery systems, including lipid-based nanoparticles, polymeric carriers, and inorganic or hybrid nanomaterials, with a focus on their structural design, drug-loading strategies, and mechanisms of action. In addition, we discuss how these platforms improve the absorption, stability, and tissue targeting of berberine. Finally, we highlight the current challenges in clinical translation, including safety, scalability, and regulatory considerations, and outline future perspectives for the rational design of nanomedicine-based berberine therapies. This review aims to provide a structured framework for guiding the development of more effective berberine delivery strategies.