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      Microneedles with Two-Stage Glucose-Sensitive Controlled Release for Long-Term Insulin Delivery

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          Abstract

          Diabetes patients cannot complete effective blood glucose regulation due to their impaired pancreatic function. At present, subcutaneous insulin injection is the only treatment for patients with type 1 and severe type 2 diabetes. However, long-term subcutaneous injection will cause patients with intense physical pain and lasting psychological burden. In addition, subcutaneous injection will lead to hypoglycemia risk to a large extent because of the uncontrollable release of insulin. In this work, we developed a glucose-sensitive microneedle patch based on phenylboronic acid (PBA)-modified chitosan (CS) particles and poly(vinyl alcohol) (PVA)/poly(vinylpyrrolidone) (PVP) hydrogel for the efficient delivery of insulin. Meanwhile, through the double glucose-sensitive response process of CS-PBA particle and external hydrogel, the sudden release of insulin was well restrained, and a more persistent blood glucose control was achieved. Finally, the painless, minimally invasive, and efficient treatment effect of the glucose-sensitive microneedle patch indicated its great advantages as a new generation of injection therapy.

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          Most cited references32

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          Hypertension and Diabetes Mellitus

          Type 2 diabetes mellitus and hypertension overlap in the population. In many subjects, development of diabetes mellitus is characterized by a relatively rapid increase in plasma glucose values. Whether a similar phenomenon occurs during the development of hypertension is not known. We analyzed the pattern of blood pressure (BP) changes during the development of hypertension in patients with or without diabetes mellitus using data from the MCDS (Mexico City Diabetes Study; a population-based study of diabetes mellitus in Hispanic whites) and in the FOS (Framingham Offspring Study, a community-based study in non-Hispanic whites) during a 7-year follow-up. Diabetes mellitus at baseline was a significant predictor of incident hypertension (in FOS, odds ratio, 3.14; 95% confidence interval, 2.17-4.54) independently of sex, age, body mass index, and familial diabetes mellitus. Conversely, hypertension at baseline was an independent predictor of incident diabetes mellitus (in FOS, odds ratio, 3.33; 95% CI, 2.50-4.44). In >60% of the converters, progression from normotension to hypertension was characterized by a steep increase in BP values, averaging 20 mm Hg for systolic BP within 3.5 years (in MCDS). In comparison with the nonconverters group, hypertension and diabetes mellitus converters shared a metabolic syndrome phenotype (hyperinsulinemia, higher body mass index, waist girth, BP, heart rate and pulse pressure, and dyslipidemia). Overall, results were similar in the 2 ethnic groups. We conclude that (1) development of hypertension and diabetes mellitus track each other over time, (2) transition from normotension to hypertension is characterized by a sharp increase in BP values, and (3) insulin resistance is one common feature of both prediabetes and prehypertension and an antecedent of progression to 2 respective disease states.
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            pH and Glucose Dual-Responsive Injectable Hydrogels with Insulin and Fibroblasts as Bioactive Dressings for Diabetic Wound Healing.

            pH and glucose dual-responsive injectable hydrogels were prepared through the cross-linking of Schiff's base and phenylboronate ester using phenylboronic-modified chitosan, poly(vinyl alcohol) and benzaldehyde-capped poly(ethylene glycol). Protein drugs and live cells could be incorporated into the hydrogels during the in situ cross-linking, displaying sustained and pH/glucose-triggered drug release from the hydrogels and cell viability and proliferation in the three-dimensional hydrogel matrix as well. Hence, the hydrogels with insulin and fibroblasts were considered as bioactive dressings for diabetic wound healing. A streptozotocin-induced diabetic rat model was used to evaluate the efficacy of hydrogel dressings in wound repair. The results revealed that the incorporation of insulin and L929 in the hydrogels could promote neovascularization and collagen deposition and enhance the wound-healing process of diabetic wounds. Thus, the drug- and cell-loaded hydrogels have promising potential in wound healing as a medicated system for various therapeutic proteins and live cells.
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              IDF Diabetes Atlas

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                Author and article information

                Contributors
                Journal
                ACS Biomaterials Science & Engineering
                ACS Biomater. Sci. Eng.
                American Chemical Society (ACS)
                2373-9878
                2373-9878
                May 08 2023
                April 07 2023
                May 08 2023
                : 9
                : 5
                : 2534-2544
                Affiliations
                [1 ]State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, P. R. China
                [2 ]Zhejiang-Russia Joint Laboratory of Photo-Electro-Magnetic Functional Materials, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, P. R. China
                [3 ]Key Laboratory of Clinical Evaluation Technology for Medical Device of Zhejiang Province, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, P. R. China
                Article
                10.1021/acsbiomaterials.3c00137
                37027835
                8b6bc7a2-63b2-48e6-a556-863dcf0feb18
                © 2023

                https://doi.org/10.15223/policy-029

                https://doi.org/10.15223/policy-037

                https://doi.org/10.15223/policy-045

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