title: Preparation of chitosan-based multifunctional nanocarriers overcoming multiple barriers for oral delivery of insulin.
abstract: To overcome multiple barriers for oral delivery of insulin, the chitosan-based multifunctional nanocarriers modified by L-valine (LV, used as a target ligand to facilitate the absorption of the small intestine) and phenylboronic acid (PBA, used as a glucose-responsive unit) have been designed and evaluated in this study. The resultant nanocarriers exhibited low cytotoxicity against HT-29 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. The chemical stability of loaded insulin against digestive enzyme were established in presence of simulated gastric fluid (SGF) containing pepsin and simulated intestinal fluid (SIF) containing pancreatin, respectively. The uptake behavior of HT-29 cells was evaluated by confocal laser scanning microscope. After oral administration to the diabetic rats, an effective hypoglycemic effect was obtained compared with subcutaneous injection of insulin. This work suggests that L-valine modified chitosan-based multifunctional nanocarriers may be a promising drug delivery carrier for oral administration of insulin.
authors: Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
authors: Lei
authors: L
authors: Li
authors: Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China; National Engineering Laboratory for Textile Fiber Materials and Processing Technology (Zhejiang), Hangzhou 310018, China; Key Laboratory of Advanced Textile Materials and Manufacturing Technology (ATMT), Ministry of Education, Hangzhou 310018, China. Electronic address: ghjiang_cn@zstu.edu.cn.
authors: Guohua
authors: G
authors: Jiang
authors: Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
authors: Weijiang
authors: W
authors: Yu
authors: Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
authors: Depeng
authors: D
authors: Liu
authors: Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
authors: Hua
authors: H
authors: Chen
authors: Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
authors: Yongkun
authors: Y
authors: Liu
authors: Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
authors: Zaizai
authors: Z
authors: Tong
authors: College of Life Science, Zhejiang Sci Tech University, Hangzhou 310018, China.
authors: Xiangdong
authors: X
authors: Kong
authors: Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China; National Engineering Laboratory for Textile Fiber Materials and Processing Technology (Zhejiang), Hangzhou 310018, China; Key Laboratory of Advanced Textile Materials and Manufacturing Technology (ATMT), Ministry of Education, Hangzhou 310018, China.
authors: Juming
authors: J
authors: Yao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D000067493:Dynamic Light Scattering; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D019073:HT29 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017207:Rats, Sprague-Dawley
chemical_list: D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D048271:Chitosan
keywords: Chitosan; Hypoglycemic effect; Insulin; Nanocarriers; Oral delivery