1.O.7.  The Coptidis Rhizoma Extract Nano-Drug Delivery System (CR-ND) Family 

The CR-ND had an average diameter of 167 nm and a Zeta potential of -12.5 mV. These nanoparticles (NPs) are formed by denaturation of co-existing plant proteins with molecular weight < 30 kDa. The NPs adsorbed or dispersed , thereby promoting berberine hydrochloride (BBR) transformation from crystal to amorphous form and improving its solubility and dissolution. The NPs carry and promote BBR uptake by human colonic adenocarcinoma (Caco-2) cells via caveolae-mediated endocytosis, reducing P-gp-mediated efflux of BBR in mice gut sacs and Madin-Darby canine kidney cells stably expressing the transporter P-gp in MDCK-MDR1 cells. Moreover, the NPs improved BBR metabolic stability in mouse intestinal S9, promoting BBR intestinal absorption, as shown by increased peak BBR concentration (Cmax, 1180 vs 310 ng/mL) and exposure level (AUC0-12 h, 2.8 vs 1.4 mg.h/mL) in mouse portal vein. The NPs increased BBR exposure levels in mouse livers (95 vs 44 mg.h/g liver). Thus, the proteinaceous nanoparticles isolated from Coptidis Rhizoma extracts can form a natural nano-drug delivery system with BBR, thereby improving the pharmacokinetics of oral BBR.