title: Multifunctional Composite Microcapsules for Oral Delivery of Insulin.
abstract: In this study, we designed and developed a new drug delivery system of multifunctional composite microcapsules for oral administration of insulin. Firstly, in order to enhance the encapsulation efficiency, insulin was complexed with functional sodium deoxycholate to form insulin-sodium deoxycholate complex using hydrophobic ion pairing method. Then the complex was encapsulated into poly(lactide-co-glycolide) (PLGA) nanoparticles by emulsion solvent diffusion method. The PLGA nanoparticles have a mean size of 168 nm and a zeta potential of -29.2 mV. The encapsulation efficiency was increased to 94.2% for the complex. In order to deliver insulin to specific gastrointestinal regions and reduce the burst release of insulin from PLGA nanoparticles, hence enhancing the bioavailability of insulin, enteric targeting multifunctional composite microcapsules were further prepared by encapsulating PLGA nanoparticles into pH-sensitive hydroxypropyl methyl cellulose phthalate (HP55) using organic spray-drying method. A pH-dependent insulin release profile was observed for this drug delivery system in vitro. All these strategies help to enhance the encapsulation efficiency, control the drug release, and protect insulin from degradation. In diabetic fasted rats, administration of the composite microcapsules produced a great enhancement in the relative bioavailability, which illustrated that this formulation was an effective candidate for oral insulin delivery.
authors.affiliation: Key Laboratory of Chemical Engineering Process and Technology for High-Efficiency Conversion, School of Chemistry and Material Science, College of Heilongjiang Province (Heilongjiang University), Heilongjiang University, Harbin 150080, China. sunshaoping111@163.com.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Sun
authors.affiliation: College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin 150025, China. liangna528@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Liang
authors.affiliation: Key Laboratory of Chemical Engineering Process and Technology for High-Efficiency Conversion, School of Chemistry and Material Science, College of Heilongjiang Province (Heilongjiang University), Heilongjiang University, Harbin 150080, China. gongxianfeng@sina.com.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Gong
authors.affiliation: Institute of Tumor Research, Harbin Medical University, Harbin 150080, China. 13766855349@139.com.
authors.forename: Weiwei
authors.initials: W
authors.lastname: An
authors.affiliation: School of Pharmaceutical Science, Aichi Gakuin University, Nagoya 470-0195, Japan. sykawa123@163.com.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. syphucuifude@163.com.
authors.forename: Fude
authors.initials: F
authors.lastname: Cui
authors.affiliation: Key Laboratory of Chemical Engineering Process and Technology for High-Efficiency Conversion, School of Chemistry and Material Science, College of Heilongjiang Province (Heilongjiang University), Heilongjiang University, Harbin 150080, China. yanpf@vip.sina.com.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Yan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002214:Capsules / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D065546:Drug Liberation; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002214:Capsules; D007328:Insulin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate
keywords: HP55; PLGA nanoparticles; insulin; microcapsules; sodium deoxycholate