title: Eudragit S100-Coated Chitosan Nanoparticles Co-loading Tat for Enhanced Oral Colon Absorption of Insulin.
abstract: In order to improve oral absorption of insulin, especially the absorption at the colon, Eudragit S100® (ES)-coated chitosan nanoparticles loading insulin and a trans-activating transcriptional peptide (Tat) were employed as the vehicle. In vitro releases of insulin and Tat from ES-coated chitosan nanoparticles had a pH-dependant characteristic. A small amount of the contents was released from the coated nanoparticles at pH 1.2 simulated gastric fluid, while a fairly fast and complete release was observed in pH 7.4 medium. Caco-2 cell was used as the model of cellular transport and uptake studies. The results showed that the cellular transport and uptake of insulin for ES-coated chitosan nanoparticles co-loading insulin and Tat (ES-Tat-cNPs) were about 3-fold and 4-fold higher than those for the nanoparticles loading only insulin (ES-cNPs), respectively. The evaluations in vivo of ES-Tat-cNPs were conducted on diabetic rats and normal minipigs, respectively. The experimental results on rats revealed that the pharmacodynamical bioavailability of ES-Tat-cNPs had 2.16-fold increase compared with ES-cNPs. After oral administration of nanoparticle suspensions to the minipigs, insulin bioavailability of ES-Tat-cNPs was 1.73-fold higher than that of ES-cNPs, and the main absorption site of insulin was probably located in the colon for the two nanoparticles. In summary, this report provided an exploratory means for the improvement of oral absorption of insulin.
authors.affiliation: School of Pharmacy, Nanchang University, Nanchang, 330006, China.
authors.forename: Shuangxi
authors.initials: S
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Nanchang University, Nanchang, 330006, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: School of Pharmacy, Nanchang University, Nanchang, 330006, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Deng
authors.affiliation: School of Pharmacy, Nanchang University, Nanchang, 330006, China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Nanchang University, Nanchang, 330006, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Nanchang University, Nanchang, 330006, China. zhonghj@ncu.edu.cn.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Jiangxi Institute of Materia Medica, Nanchang, 330006, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.affiliation: Jiangxi Institute of Materia Medica, Nanchang, 330006, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Luo
authors.affiliation: State Key Lab of Food Science and Technology, Food College of Nanchang University, Nanchang, 330006, China.
authors.forename: Zeyuan
authors.initials: Z
authors.lastname: Deng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D057846:Cell-Penetrating Peptides; D048271:Chitosan; D003106:Colon / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011109:Polymethacrylic Acids; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D011109:Polymethacrylic Acids; D054322:tat Gene Products, Human Immunodeficiency Virus; C038300:methylmethacrylate-methacrylic acid copolymer; D048271:Chitosan
keywords: Eudragit S100; Tat; chitosan nanoparticles; insulin; oral colon delivery