Injectable dual glucose-responsive hydrogel-micelle composite for mimicking physiological basal and prandial insulin delivery

论文摘要

For type 1 and advanced type 2 diabetic patients, insulin replacement therapy with simulating on-demand prandial and basal insulin secretion is the best option for optimal glycemic control. However, there is no insulin delivery system yet could mimic both controlled basal insulin release and rapid prandial insulin release in response to real-time blood glucose changes. Here we reported an artificial insulin delivery system, mimicking physiological basal and prandial insulin secretion, to achieve real-time glycemic control and reduce risk of hypoglycemia. A phenylboronic acid（PBA）/galactosyl-based glucose-responsive insulin delivery system was prepared with insulin-loaded micelles embedded in hydrogel matrix. At the hyperglycemic state, both the hydrogel and micelles could swell and achieve rapid glucose-responsive release of insulin, mimicking prandial insulin secretion.When the glucose level returned to the normal state, only the micelles partially responded to glucose and still released insulin gradually. The hydrogel with increased crosslinking density could slow down the diffusion speed of insulin inside, resulting in controlled release of insulin and simulating physiological basal insulin secretion. This hydrogel-micelle composite insulin delivery system could quickly reduce the blood glucose level in a mouse model of type 1 diabetes, and maintain normal blood glucose level without hypoglycemia for about 24 h. This kind of glucose-responsive hydrogel-micelle composite may be a promising candidate for delivery of insulin in the treatment of diabetes.

论文目录

1 Introduction

2 Experimental

2.1 Materials

2.2 Synthesis and characterization of PEG-b-P （Asp-co-AspAPBA）

2.3 Synthesis of glycopolymer P （Asp-co-AspGal）

2.4 Synthesis ofγ-P （GA-co-GAGal）

2.5 Synthesis of P （Lys-co-LysFCPBA） -b-PEG-b-P （Lys-co-LysFCPBA）

2.6 Preparation and characterization of insulin-loaded micelles

2.7 In vitro glucose-responsive insulin release from micelles

2.8 Preparation of insulin-loaded hydrogel-micelle composite （or hydrogel） and in vitro insulin release

2.9 Scanning electron microscope （SEM） measure-ments

2.1 0 Evaluation of rheological behavior

2.1 1 In vivo studies using streptozotocin-induced dia-betic mice

2.1 2 Biocompatibility analysis

3 Results and discussion

3.1 Formation and characterization of insulin-loaded micelles

3.2 Formation and characterization of the hydrogel

3.3 In vitro glucose-responsive insulin release of hy-drogel-micelle composite

3.4 In vivo studies of the insulin-loaded hydrogel-micelle composite for type 1 diabetes treatment

4 Conclusions

文章来源

类型: 期刊论文

作者: Juan Lv,Gang Wu,Ying Liu,Chang Li,Fan Huang,Yumin Zhang,Jinjian Liu,Yingli An,Rujiang Ma,Linqi Shi

来源: Science China(Chemistry) 2019年05期

年度: 2019

分类: 工程科技Ⅰ辑,医药卫生科技

专业: 化学,内分泌腺及全身性疾病

单位: State Key Laboratory of Medicinal Chemical Biology,Key Laboratory of Functional Polymer Materials of Ministry of Education,Institute of Polymer Chemistry,College of Chemistry,Nankai University,Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine,Institute of Radiation Medicine,Chinese Academy of Medical Science & Peking Union Medical College,Collaborative Innovation Center of Chemical Science and Engineering (Tianjin),Nankai University

基金: supported by the National Natural Science Foundation of China(51603105,51773099,51390483,91527306,21620102005),the Program for Changjiang Scholars and Innovative Research Team in University(IRT1257)

分类号: O648.17;R587.1

页码: 637-648

总页数: 12

文件大小: 802K

下载量: 20

Injectable dual glucose-responsive hydrogel-micelle composite for mimicking physiological basal and prandial insulin delivery

论文摘要

论文目录

文章来源

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