A composite hydrogel system containing glucose-responsive nanocarriers for oral delivery of insulin.
Development of an oral delivery strategy for insulin therapeutics has drawn much attention in recent years. In this study, a glucose-responsive nanocarriers for loading of insulin has been prepared firstly. The resultant nanocarriers exhibited relative low cytotoxicity against Caco-2 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. In order to enhance the oral bioavailability of insulin, the insulin-loaded glucose-responsive nanocarriers were further encapsulated into a three-dimensional (3D) hyaluronic acid (HA) hydrogel environment for overcoming multiple barriers and providing multi-protection for insulin during the transport process. The hypoglycemic effect for oral delivery of insulin was studied in vivo. After oral administration to the diabetic rats, the released insulin from hydrogel systems containing insulin-loaded glucose-responsive nanocarriers exhibited an effective hypoglycemic effect for longer time compared with insulin-loaded nanocarriers.
Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
Lei
L
Li
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.
Guohua
G
Jiang
Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
Weijiang
W
Yu
Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
Depeng
D
Liu
Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
Hua
H
Chen
Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
Yongkun
Y
Liu
Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
Qin
Q
Huang
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.
Zaizai
Z
Tong
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.
Juming
J
Yao
College of Life Science, Zhejiang Sci Tech University, Hangzhou 310018, China.
Xiangdong
X
Kong
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D000067493:Dynamic Light Scattering; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry*; D008297:Male; D053761:Nanocomposites / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid
Hydrogel; Hypoglycemic effect; Insulin; Nanocarriers; Oral delivery