title: Insulin-S.O (sodium oleate) complex-loaded PLGA nanoparticles: formulation, characterization and in vivo evaluation.
abstract: S.O (sodium oleate) is an anionic surfactant, which is able to forman ionic complex with positively charged insulin at suitable pH. In a previous study, the insulin-S.O (Ins-S.O) complex was prepared by a hydrophobic ion pairing (HIP) method to improve the apparent liposolubility of insulin. The formation of the complex was further confirmed by Zeta potential and X-ray method. Based on the preliminary study, poly(lactide-co-glycolide) (PLGA) nanoparticles harbouring Ins-S.O complex was prepared via an emulsion solvent diffusion method. The effects of key parameters such as concentration of PVA, concentration of PLGA and initial-loaded drug on the properties of the nanoparticles were investigated. The insulin encapsulation efficiency (EE(%)) reached up to 91.2% and mean diameter of the nanoparticles was sized approximately 160 nm under optimal conditions. The pharmacological effects of the nanoparticles made of PLGA (75/25, Av Mw 15,000) were further evaluated to confirm their potential suitability for oral delivery. In order to evaluate hyperglycaemic effect of the nanoparticles for oral administration, Ins-S.O complex-loaded PLGA nanoparticles (20 IU/Kg) were administered orally by force-feeding to diabetic rats. In the case of the nanoparticles, the plasma glucose level reduced to 23.85% from the initial one 12 h post-administration and this continued for 24 h. The results showed that the use of Ins-S.O complex-loaded PLGA nanoparticles is an effective method of reducing plasma glucose levels. The insulin nanoparticles also improved the glycaemic response to an oral glucose challenge.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Sun
authors.forename: Na
authors.initials: N
authors.lastname: Liang
authors.forename: Hongze
authors.initials: H
authors.lastname: Piao
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Fude
authors.initials: F
authors.lastname: Cui
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D019301:Oleic Acid / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019301:Oleic Acid; D019344:Lactic Acid; C013173:osteum