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Glucose-Responsive Silk Fibroin Microneedles for Transdermal Delivery of Insulin
Microneedles (MNs) have attracted great interest as a drug delivery alternative to subcutaneous injections for treating diabetes mellitus. We report MNs prepared from polylysine-modified cationized silk fibroin (SF) for responsive transdermal insulin delivery. Scanning electron microscopy analysis o...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944804/ https://www.ncbi.nlm.nih.gov/pubmed/36810381 http://dx.doi.org/10.3390/biomimetics8010050 |
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author | Tan, Guohongfang Jiang, Fujian Jia, Tianshuo Qi, Zhenzhen Xing, Tieling Kundu, Subhas C. Lu, Shenzhou |
author_facet | Tan, Guohongfang Jiang, Fujian Jia, Tianshuo Qi, Zhenzhen Xing, Tieling Kundu, Subhas C. Lu, Shenzhou |
author_sort | Tan, Guohongfang |
collection | PubMed |
description | Microneedles (MNs) have attracted great interest as a drug delivery alternative to subcutaneous injections for treating diabetes mellitus. We report MNs prepared from polylysine-modified cationized silk fibroin (SF) for responsive transdermal insulin delivery. Scanning electron microscopy analysis of MNs’ appearance and morphology revealed that the MNs were well arranged and formed an array with 0.5 mm pitch, and the length of single MNs is approximately 430 μm. The average breaking force of an MN is above 1.25 N, which guarantees that it can pierce the skin quickly and reach the dermis. Cationized SF MNs are pH-responsive. MNs dissolution rate increases as pH decreases and the rate of insulin release are accelerated. The swelling rate reached 223% at pH = 4, while only 172% at pH = 9. After adding glucose oxidase, cationized SF MNs are glucose-responsive. As the glucose concentration increases, the pH inside the MNs decreases, the MNs’ pore size increases, and the insulin release rate accelerates. In vivo experiments demonstrated that in normal Sprague Dawley (SD) rats, the amount of insulin released within the SF MNs was significantly smaller than that in diabetic rats. Before feeding, the blood glucose (BG) of diabetic rats in the injection group decreased rapidly to 6.9 mmol/L, and the diabetic rats in the patch group gradually reduced to 11.7 mmol/L. After feeding, the BG of diabetic rats in the injection group increased rapidly to 33.1 mmol/L and decreased slowly, while the diabetic rats in the patch group increased first to 21.7 mmol/L and then decreased to 15.3 mmol/L at 6 h. This demonstrated that the insulin inside the microneedle was released as the blood glucose concentration increased. Cationized SF MNs are expected to replace subcutaneous injections of insulin as a new modality for diabetes treatment. |
format | Online Article Text |
id | pubmed-9944804 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99448042023-02-23 Glucose-Responsive Silk Fibroin Microneedles for Transdermal Delivery of Insulin Tan, Guohongfang Jiang, Fujian Jia, Tianshuo Qi, Zhenzhen Xing, Tieling Kundu, Subhas C. Lu, Shenzhou Biomimetics (Basel) Article Microneedles (MNs) have attracted great interest as a drug delivery alternative to subcutaneous injections for treating diabetes mellitus. We report MNs prepared from polylysine-modified cationized silk fibroin (SF) for responsive transdermal insulin delivery. Scanning electron microscopy analysis of MNs’ appearance and morphology revealed that the MNs were well arranged and formed an array with 0.5 mm pitch, and the length of single MNs is approximately 430 μm. The average breaking force of an MN is above 1.25 N, which guarantees that it can pierce the skin quickly and reach the dermis. Cationized SF MNs are pH-responsive. MNs dissolution rate increases as pH decreases and the rate of insulin release are accelerated. The swelling rate reached 223% at pH = 4, while only 172% at pH = 9. After adding glucose oxidase, cationized SF MNs are glucose-responsive. As the glucose concentration increases, the pH inside the MNs decreases, the MNs’ pore size increases, and the insulin release rate accelerates. In vivo experiments demonstrated that in normal Sprague Dawley (SD) rats, the amount of insulin released within the SF MNs was significantly smaller than that in diabetic rats. Before feeding, the blood glucose (BG) of diabetic rats in the injection group decreased rapidly to 6.9 mmol/L, and the diabetic rats in the patch group gradually reduced to 11.7 mmol/L. After feeding, the BG of diabetic rats in the injection group increased rapidly to 33.1 mmol/L and decreased slowly, while the diabetic rats in the patch group increased first to 21.7 mmol/L and then decreased to 15.3 mmol/L at 6 h. This demonstrated that the insulin inside the microneedle was released as the blood glucose concentration increased. Cationized SF MNs are expected to replace subcutaneous injections of insulin as a new modality for diabetes treatment. MDPI 2023-01-24 /pmc/articles/PMC9944804/ /pubmed/36810381 http://dx.doi.org/10.3390/biomimetics8010050 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tan, Guohongfang Jiang, Fujian Jia, Tianshuo Qi, Zhenzhen Xing, Tieling Kundu, Subhas C. Lu, Shenzhou Glucose-Responsive Silk Fibroin Microneedles for Transdermal Delivery of Insulin |
title | Glucose-Responsive Silk Fibroin Microneedles for Transdermal Delivery of Insulin |
title_full | Glucose-Responsive Silk Fibroin Microneedles for Transdermal Delivery of Insulin |
title_fullStr | Glucose-Responsive Silk Fibroin Microneedles for Transdermal Delivery of Insulin |
title_full_unstemmed | Glucose-Responsive Silk Fibroin Microneedles for Transdermal Delivery of Insulin |
title_short | Glucose-Responsive Silk Fibroin Microneedles for Transdermal Delivery of Insulin |
title_sort | glucose-responsive silk fibroin microneedles for transdermal delivery of insulin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944804/ https://www.ncbi.nlm.nih.gov/pubmed/36810381 http://dx.doi.org/10.3390/biomimetics8010050 |
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