Oral GLP1 Gene Delivery by an Antibody-Guided Nanomaterial to Treat Type 2 Diabetes Mellitus
| Autor: | Yong Hwa Hwang, Sungpil Cho, Jeong Man An, Yong-kyu Lee, Mohammad Nazmul Hasan, S. M.Shatil Shahriar |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Blood Glucose
Materials science Cell Survival medicine.medical_treatment Administration Oral Succinimides Incretin Receptors Fc Gene delivery Pharmacology Hypoglycemia Diabetes Mellitus Experimental Mice Neonatal Fc receptor Glucagon-Like Peptide 1 Diabetes mellitus Intestine Small medicine Animals Tissue Distribution General Materials Science Protamines Drug Carriers Rhodamines Pancreatic islets Insulin Gene Transfer Techniques Type 2 Diabetes Mellitus medicine.disease Nanostructures medicine.anatomical_structure Immunoglobulin G Transcytosis |
| Zdroj: | ACS Applied Materials & Interfaces. 12:38925-38935 |
| ISSN: | 1944-8252 1944-8244 |
| Popis: | Type 2 diabetes mellitus (T2DM) is a chronic and progressive hyperglycemic condition. Glucagon-like peptide-1 (GLP1) is an incretin secreted from pancreatic β-cells and helps to produce insulin to balance the blood glucose level without the risk of hypoglycemia. However, the therapeutic application of GLP1 is limited by its intrinsic short half-life and rapid metabolic clearance in the body. To enhance the antidiabetic effect of GLP1, we designed a human cysteine-modified IgG1-Fc antibody-mediated oral gene delivery vehicle, which helps to produce GLP1 sustainably in the target site with the help of increased half-life of the Fc-conjugated nanocarrier, protects GLP1 from acidic and enzymatic degradation in the gastrointestinal (GI) tract, uptakes and transports the GLP1 formulation through the neonatal Fc receptor (FcRn), and helps to release the GLP1 gene in the intestine. Our formulation could reduce the blood glucose from about an average of 320 mg/dL (hyperglycemic) to 150 mg/dL (normal blood glucose concentration) in diabetic mice, which is about 50% reduction of the total blood glucose concentration. GLP1 (500 μg) complexed with the IgG1-Fc carrier was proven to be the optimal dose for a complete reduction of hyperglycemic conditions in diabetic mice. A significant amount of insulin production and the presence of GLP1 peptide were observed in the pancreatic islets of oral GLP1 formulation-treated diabetic mice in immunohistochemistry analysis compared to nontreated diabetic mice. The orally given formulation was completely nontoxic according to the histopathology analysis of mice organ tissues, and no mice death was observed. Our antibody-mediated oral gene delivery system is a promising tool for various oral therapeutic gene delivery applications to treat diseases like diabetes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|