Pharmacological activities of berberine and strategies to improve its oral bioavailability / 药学学报

Berberine is a naturally occurring benzylisoquinoline alkaloid with a wide range of pharmacological activities, such as antibacterial, anticancer, hypolipidemic, antidiabetic and antidiarrheal. Although berberine has a wide range of curative effects, the extremely low bioavailability (< 1%) limits its clinical application. Pure berberine preparations have not yet been approved for any specific disease. The low oral bioavailability of berberine is mainly due to poor solubility caused by self-aggregation under acidic conditions, low permeability, P-glycoprotein (P-gp)-mediated efflux, and liver and intestine metabolism. To improve the oral bioavailability of berberine, researchers have adopted a variety of strategies, including the application of various nano-delivery systems, penetration enhancers and P-gp inhibitors, structural modifications, and development of berberine derivatives. Improving the oral bioavailability of berberine can improve the pharmacological activity of berberine, reduce the dosage, and then reduce the toxic and side effects. This review summarized the various pharmacological activities, metabolism progress and pharmacokinetic characteristics of berberine, the newly discovered berberine target intestinal microbiota and focused on the strategies to improve the oral bioavailability of berberine by improving solubility and permeability, inhibiting P-gp efflux, and structural modification. The research on berberine was prospected, which provided guidance for the in-depth study of berberine.

Advances in nanocrystal technology and its application to improve the pharmacological efficacy for poorly-water soluble drugs / 药学学报

In order to solve the problems of erratic drug absorption and low bioavailability after oral administration for poorly-water soluble drugs due to low solubility, a series of novel pharmaceutical dosage forms as solid dispersion, liposome, microemulsion, vesicle, cyclodextrin inclusion complexes and drug nanocrystal have been developed in recent years. Among which drug nanocrystal attracts more attentions for its simpler preparation method, higher drug loading and easier manufacturing technology in the design of dosage forms suitable for different administration routes. In this paper, the nanocrystals of the poorly-water soluble drugs prepared based on bottom-up and top-down technologies were introduced. The characteristics and applications of the nanocrystal-based dosage forms as suspension, tablet and capsule were also introduced and carefully evaluated with the focus on their pharmacokinetics, pharmacodynamics and tissue targeted drug distribution after delivery by oral administration, intravenous injection and pulmonary inhalation. The advantages of drug nanocrystals in their therapeutics effects over the bulk drugs were discussed together with the inherent mechanism. Finally, the problems existing in basic research and scaled-up manufacture of drug nanocrystal as well as the possible ways of solution were listed out so as to make the nanocrystal-based preparations exert their maximum therapeutic effect after clinical application.