title: pH-sensitive peptide hydrogel for glucose-responsive insulin delivery.
abstract: Glucose-responsive system is one of important options for self-regulated insulin delivery to treat diabetes, which has become an issue of great public health concern in the world. In this study, we developed a novel and biocompatible glucose-responsive insulin delivery system using a pH-sensitive peptide hydrogel as a carrier loaded with glucose oxidase, catalase and insulin. The peptide could self-assemble into hydrogel under physiological conditions. When hypoglycemia is encountered, neighboring alkaline amino acid side chains are significantly repulsed due to reduced local pH by the enzymatic conversion of glucose into gluconic acid. This is followed by unfolding of individual hairpins, disassembly and release of insulin. The glucose-responsive hydrogel system was characterized on the basis of structure, conformation, rheology, morphology, acid-sensitivity and the amount of consistent release of insulin in vitro and vivo. The results illustrated that our system can not only regulate the blood glucose levels in vitro but also in mice models having STZ-induced diabetes.
  
  
  
  In this report, we have shown the following significance supported by the experimental results. 1. We successfully developed, characterized and screened a novel pH-responsive peptide. 2. We successfully developed a novel and biocompatible pH-sensitive peptide hydrogel as glucose-responsive insulin delivery system loaded with glucose oxidase, catalase and insulin. 3. We successfully confirmed that the hydrogel platform could regulate the blood glucose level in vitro and in vivo. Overall, we have shown enough significance and novelty with this smart hydrogel platform in terms of biomaterials, peptide chemistry, self-assembly, hydrogel and drug delivery. So we believe this manuscript is suitable for Acta Biomaterialia.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Mian
authors.initials: M
authors.lastname: Fu
authors.affiliation: Key Laboratory of Sensing Technology and Biomedical Instrument of Guang Dong Province, School of Engineering, Sun Yat-sen University, Guangzhou 510006, PR China; Key Laboratory for Polymeric Composite & Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510006, PR China. Electronic address: wujun29@mail.sysu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.affiliation: University of Waterloo, 200 University Ave W, Waterloo, ON N2L 3G1, Canada.
authors.forename: Arvind
authors.initials: A
authors.lastname: Dhinakar
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China; Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: qianhai24@163.com.
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: geliang1981@hotmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Ge
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D005947:Glucose / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D010455:Peptides / Q000737:chemistry; D012996:Solutions
chemical_list: D007328:Insulin; D010455:Peptides; D012996:Solutions; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D016650:Fluorescein-5-isothiocyanate; D005947:Glucose
keywords: Diabetes; Glucose-responsive; Insulin-delivery; Self-assembly peptide hydrogels