title: Preparation of an anhydrous reverse micelle delivery system to enhance oral bioavailability and anti-diabetic efficacy of berberine.
abstract: To enhance oral bioavailability and anti-diabetic efficacy of berberine (BER), an anhydrous reverse micelle (ARM) delivery system was prepared through lyophilization of water-in-oil (W/O) emulsions. Using soy phosphatidylcholine as emulsifiers, BER-containing W/O emulsions were prepared and then lyophilized to form dry products which, upon addition of oil, formed clear ARMs containing amorphous BER nanoparticles. BER-loaded ARMs or free BER solutions were administered to streptozocin-induced diabetic mice. In vivo measurements demonstrated that the blood glucose levels (BGLs) of diabetic mice reduced on average to 22% of the initial values 4h after intravenous injection of BER solution at the dose of 2.5mg/kg body weight, while the average BGL reduction was 57% in the group gavaged with ARMs at the dose of 100mg/kg body weight. No significant BGL reduction was noticed in mice orally received BER solutions. Compared to BER solutions, the oral bioavailability of BER-loaded ARMs was enhanced 2.4-fold, and the maximum blood concentration of BER was enhanced 2.1-fold with a 2-h time lag leading to a prolonged efficacy. Thus, this novel ARM delivery system provides a valid method to improve oral bioavailability and anti-diabetic efficacy of BER, offering a promising product alternative to other hypoglycemic drugs for diabetes therapy.
authors: Department of Pharmacy, Jining Medical College, 669 Xueyuan Road, Sunshine City, Shandong Province, China. twangcn@yahoo.com
authors: Ting
authors: T
authors: Wang
authors: Ning
authors: N
authors: Wang
authors: Hui
authors: H
authors: Song
authors: Xiaonan
authors: X
authors: Xi
authors: JianAn
authors: J
authors: Wang
authors: Aijun
authors: A
authors: Hao
authors: Tiefu
authors: T
authors: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001599:Berberine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis; D003460:Crystallization; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D004655:Emulsions; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008027:Light; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008823:Micelles; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D009061:Mouth Mucosa / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012542:Scattering, Radiation; D012995:Solubility; D013311:Streptozocin / Q000494:pharmacology; D013499:Surface Properties
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D004655:Emulsions; D007004:Hypoglycemic Agents; D008823:Micelles; D001599:Berberine; D013311:Streptozocin