Bioavailability of berberine: challenges and solutions

Abstract

Berberine is a quaternary benzylisoquinoline alkaloid with multiple pharmacological effects used for the treatment of hypertension, tumors, bacterial infections, inflammation, HIV, and cardiac diseases. In phase I clinical trials, berberine is safe at excessive doses but manifests poor bioavailability. Major challenges like poor absorption, rapid metabolism, and rapid systemic elimination are responsible for low plasma and tissue levels of berberine. Various strategies have been undertaken by several researchers to overcome this issue and enhance the bioavailability of berberine. This includes the design of new formulation strategies; novel drug delivery systems (NDDS) like liposomes, nanosized dosage forms, phospholipid complexes, mucoadhesive microparticles, and micoemulsions; the use of adjuvants; and the design of structural analogous of berberine. This review focuses on the occurrence of berberine in numerous plants and its pharmacological activities as evidenced through numerous preclinical and clinical studies. The later part of this review highlights the bioavailability issue of berberine which arises due to its poor absorption, elevated rate and extent of metabolism, and quick elimination and clearance from the body. A systematic effort has beenmade to analyze the various formulation strategies, including the design of newer berberine analogues and derivatives. These strategies can be further explored to increase the bioavailability, medicinal value, and application of this promising molecule.