Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles

Abstract

The high aqueous solubility, poor permeability, and absorption of berberine (BBR) result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs) were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm), zeta potential (7.87 mV), encapsulation efficiency (58%), and drug loading (4.2%). The power of X-ray diffraction combined with 1 H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg) oral pharmacokinetic studies in rats showed significant improvement ( P <0.05) in the peak plasma concentration, area under the curve, and variance of mean residence time of BBR-SLNs when compared to BBR alone ( P <0.05), suggesting improved bioavailability. Furthermore, oral administration of both BBR and BBR-SLNs significantly suppressed body weight gain, fasting blood glucose levels, and homeostasis assessment of insulin resistance, and ameliorated impaired glucose tolerance and insulin tolerance in db/db diabetic mice. BBR-SLNs at high dose (100 mg/kg) showed more potent effects when compared to an equivalent dose of BBR. Morphologic analysis demonstrated that BBR-SLNs potentially promoted islet function and protected the islet from regeneration. In conclusion, our study demonstrates that by entrapping BBR into SLNs the absorption of BBR and its anti-diabetic action were effectively enhanced.

Effects of Chelidonium majus extracts and major alkaloids on hERG potassium channels and on dog cardiac action potential — A safety approach

“…Appropiate cardiac risk estimation of hydroalcoholic extracts of the high aqueous solubility, poor permeability, and absorption of berberine result in its low plasma level. It was reported that the maximum concentration (C max ) of berberine in the plasma was 11 ng/ml after a single intragastric administration of 50 mg/kg [16], and 26 ng/ml after a single dose of 200 mg/kg [17] to rats. In humans, the value of C max was only 0.4 ng/ml after a single oral dose of 400 mg berberine [18], indicating limited gastrointestinal berberine absorption.…”

Berberine-loaded solid lipid nanoparticles are concentrated in the liver and ameliorate hepatosteatosis in db/db mice

“…BBR-SLNs were prepared using our patented method 16 and details were listed in our previous study. 9 The composition of the blank nanoparticles is a mixture of glycerol tripalmitate and soybean phospholipid (1:1). All other reagents were high-performance liquid chromatography grade, or they were of the highest purity commercially available.…”

“…The chromatographic system and instrumentation for detection were prepared as previously described. 9 Measurement of serum alT, asT, NeFa levels, and liver Tg content…”

“…9 Furthermore, the oral administration of BBR-SLNs significantly suppressed body weight increases, fasting blood glucose levels, the homeostasis assessment of insulin resistance, and it ameliorated impaired glucose tolerance and insulin tolerance in db/db mice. 9 Nonalcoholic fatty liver disease (NAFLD) has been recognized as a major health issue.…”

“…9 Furthermore, the oral administration of BBR-SLNs significantly suppressed body weight increases, fasting blood glucose levels, the homeostasis assessment of insulin resistance, and it ameliorated impaired glucose tolerance and insulin tolerance in db/db mice. 9 Nonalcoholic fatty liver disease (NAFLD) has been recognized as a major health issue. 10 It is caused by excess liver lipid accumulation, hepatic inflammation, hepatic insulin resistance, and nonalcoholic steatohepatitis that usually culminates in hepatic fibrosis or cirrhosis.…”