title: Preparation, characterization, and evaluation in vivo of Ins-SiO₂-HP55 (insulin-loaded silica coating HP55) for oral delivery of insulin.
abstract: Insulin is the most effective and durable drug in the treatment of advanced stage diabetes. However, oral delivering insulin was a tough task for rapid enzymatic degradation. In this work, we designed and developed a delivery system composed of enteric nanosphere for oral delivery of insulin. The silica was selected for loading insulin, which surface has a lot of pores with a powerful adsorption capacity, advantages for permeability and slow-release. The insulin-loaded silica (Ins-SiO2) was prepared by adsorption in HCl solution. The Ins-SiO2 obtained was coated with the hydroxypropyl methylcellulose phthalate (HP55) by desolvation method, which is a good enteric coating material. The Ins-SiO2-HP55, an enteric nanosphere of insulin obtained were characterized by transmission electron microscope (TEM), surface area, Fourier-transform infrared (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The results showed that insulin was loaded most in the pores of silica, while the HP55 coated on the extent of Ins-SiO2. In vitro drug release results revealed that the release of insulin from Ins-SiO2-HP55 was markedly reduced in simulated gastric fluid (SGF). By contrast, the release amount of insulin from Ins-SiO2-HP55 was increased significantly in simulated intestinal fluid (SIF). In vivo evaluation on diabetic animals showed the blood glucose level of diabetic rats could be effectively reduced after oral administration Ins-SiO2-HP55. There is marked hypoglycemic effect after 1h of taking the Ins-SiO2-HP55. After 3h, the GLU of rats of the Ins-SiO2-HP55 stably kept from 4.85 to 2.67 mmol/L that was significantly less than the normal level (6.7 mmol/L). However, that of rats taking raw insulin kept from 8.03 to 6.56 mmol/L that is higher than the normal level. These results suggested that Ins-SiO2-HP55 could have potential value in oral administration systems of diabetes chemotherapy.
authors.affiliation: Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Zhao
authors.forename: Chang
authors.initials: C
authors.lastname: Shan
authors.forename: Yuangang
authors.initials: Y
authors.lastname: Zu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weiguo
authors.initials: W
authors.lastname: Wang
authors.forename: Kunlun
authors.initials: K
authors.lastname: Wang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Sui
authors.forename: Ruiqiang
authors.initials: R
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000327:Adsorption; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004337:Drug Carriers; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D054118:Nanospheres; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013818:Thermogravimetry; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D012822:Silicon Dioxide; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate
keywords: Controlled release; Enteric capsule; In vivo evaluation; Insulin; Oral delivery; Silica