Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care
One of the most effective treatments for diabetes is to design a glucose-regulated insulin (INS) delivery system that could adjust the INS release time and rate to reduce diabetes-related complications. Here, mixed multiple layer-by-layer (mmLbL)-INS microspheres were developed for glucose-mediated...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.996763/full |
| _version_ | 1811257855238471680 |
|---|---|
| author | Yanguang Yang Xiangqian Wang Xiaopeng Yuan Qiwei Zhu Shusen Chen Donglin Xia |
| author_facet | Yanguang Yang Xiangqian Wang Xiaopeng Yuan Qiwei Zhu Shusen Chen Donglin Xia |
| author_sort | Yanguang Yang |
| collection | DOAJ |
| description | One of the most effective treatments for diabetes is to design a glucose-regulated insulin (INS) delivery system that could adjust the INS release time and rate to reduce diabetes-related complications. Here, mixed multiple layer-by-layer (mmLbL)-INS microspheres were developed for glucose-mediated INS release and an enhanced hypoglycemic effect for diabetes care. To achieve ultrafast glucose-activated INS release, glucose oxidase (GOx) was assembled with a positively charged polymer and modified on INS LbL. The mmLbL-INS microspheres were constructed with one, two, and four layers of the polyelectrolyte LbL assembly at a ratio of 1:1:1. Under hyperglycemia, GOx converts a change in the hyperglycemic environment to a pH stimulus, thus providing sufficient hydrogen ion. The accumulated hydrogen ion starts LbL charge shifting, and anionic polymers are converted to cationic polymers through hydrolytic cleavage of amine-functionalized side chains. The results of in vitro INS release suggested that glucose can modulate the mmLbL-INS microspheres in a pulsatile profile. In vivo studies validated that this formulation enhanced the hypoglycemic effect in STZ-induced diabetic rats within 2 h of subcutaneous administration and facilitated stabilization of blood glucose levels for up to 2 days. This glucose-activatable LbL microsphere system could serve as a powerful tool for constructing a precisely controlled release system. |
| first_indexed | 2024-04-12T18:04:03Z |
| format | Article |
| id | doaj.art-23f37deab01e4db6805924c0e6e292fd |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-12T18:04:03Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-23f37deab01e4db6805924c0e6e292fd2022-12-22T03:22:02ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-09-011010.3389/fbioe.2022.996763996763Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes careYanguang Yang0Xiangqian Wang1Xiaopeng Yuan2Qiwei Zhu3Shusen Chen4Donglin Xia5Department of Radiotherapy, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, ChinaDepartment of Radiotherapy, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, ChinaDepartment of Radiotherapy, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, ChinaDepartment of Radiotherapy, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, ChinaDepartment of Radiotherapy, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, ChinaSchool of Public Health, Nantong University, Nantong, ChinaOne of the most effective treatments for diabetes is to design a glucose-regulated insulin (INS) delivery system that could adjust the INS release time and rate to reduce diabetes-related complications. Here, mixed multiple layer-by-layer (mmLbL)-INS microspheres were developed for glucose-mediated INS release and an enhanced hypoglycemic effect for diabetes care. To achieve ultrafast glucose-activated INS release, glucose oxidase (GOx) was assembled with a positively charged polymer and modified on INS LbL. The mmLbL-INS microspheres were constructed with one, two, and four layers of the polyelectrolyte LbL assembly at a ratio of 1:1:1. Under hyperglycemia, GOx converts a change in the hyperglycemic environment to a pH stimulus, thus providing sufficient hydrogen ion. The accumulated hydrogen ion starts LbL charge shifting, and anionic polymers are converted to cationic polymers through hydrolytic cleavage of amine-functionalized side chains. The results of in vitro INS release suggested that glucose can modulate the mmLbL-INS microspheres in a pulsatile profile. In vivo studies validated that this formulation enhanced the hypoglycemic effect in STZ-induced diabetic rats within 2 h of subcutaneous administration and facilitated stabilization of blood glucose levels for up to 2 days. This glucose-activatable LbL microsphere system could serve as a powerful tool for constructing a precisely controlled release system.https://www.frontiersin.org/articles/10.3389/fbioe.2022.996763/fullglucose-activitydiabetesinsulincharge shiftinglayer-by-layer |
| spellingShingle | Yanguang Yang Xiangqian Wang Xiaopeng Yuan Qiwei Zhu Shusen Chen Donglin Xia Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care Frontiers in Bioengineering and Biotechnology glucose-activity diabetes insulin charge shifting layer-by-layer |
| title | Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care |
| title_full | Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care |
| title_fullStr | Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care |
| title_full_unstemmed | Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care |
| title_short | Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care |
| title_sort | glucose activatable insulin delivery with charge conversional polyelectrolyte multilayers for diabetes care |
| topic | glucose-activity diabetes insulin charge shifting layer-by-layer |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.996763/full |
| work_keys_str_mv | AT yanguangyang glucoseactivatableinsulindeliverywithchargeconversionalpolyelectrolytemultilayersfordiabetescare AT xiangqianwang glucoseactivatableinsulindeliverywithchargeconversionalpolyelectrolytemultilayersfordiabetescare AT xiaopengyuan glucoseactivatableinsulindeliverywithchargeconversionalpolyelectrolytemultilayersfordiabetescare AT qiweizhu glucoseactivatableinsulindeliverywithchargeconversionalpolyelectrolytemultilayersfordiabetescare AT shusenchen glucoseactivatableinsulindeliverywithchargeconversionalpolyelectrolytemultilayersfordiabetescare AT donglinxia glucoseactivatableinsulindeliverywithchargeconversionalpolyelectrolytemultilayersfordiabetescare |