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Application of Bioresponsive Polymers in Drug Delivery
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Manisha Lalan, Deepti Jani, Pratiksha Trivedi, Deepa H. Patel
Glucagon-like peptide-1 (GLP-1) is an incretin peptide of the endocrine L-cells of the intestinal mucosa with unique antidiabetic potential. Although the molecule has tremendous potential, its low absorption efficiency and instability in the gastrointestinal tract becomes a challenge for its oral delivery. A novel silica-based pH-sensitive nanomatrix of GLP-1 was developed which was composed of silica nanoparticles and pH-sensitive Eudragit®. The cell line studies, pharmacokinetics, and intraperitoneal glucose tolerance test, toxicological evaluations validated its success. Another study on mesoporous silica nanoparticles (MSPs) with surface positive charges could entrap anionic molecules. The entrapped drugs were not released in acidic pH and released only in the neutral intestinal pH [42, 43].
Pharmaceutical Applications of Albumin
Published in Amit Kumar Nayak, Md Saquib Hasnain, Dilipkumar Pal, Natural Polymers for Pharmaceutical Applications, 2019
The circulatory half-life of human GLP-1 is normally 1–2 min (Halpern et al., 2002; Ahrén et al., 2009). The GLP-1 fusion, albiglutideTM, is a protease-resistant GLP-1 receptor agonist made up of two repeats of the protease-resistant derivative of GLP-1 directly fused to the N-terminus of recombinant human albumin. Series of clinical trials with multiple biweekly or once-weekly injections of albiglutide shows safety, tolerability, and increased half-life (~5 days) (Madsbad et al., 2011). The G-CSF-fusion, balugrastim is comprised of granulocyte colony-stimulating factor protein directly linked to the C-terminus of albumin. Pre-clinical studies in mice and cynomolgus monkeys also showed the efficacy, well tolerability and increased the half-life of balugrastim in comparison to the unfused molecule (Halpern et al., 2002; Bock et al., 2010; Volovat et al., 2014).
Nanobiomaterial for Non-Viral Gene Delivery
Published in Anil K. Sharma, Raj K. Keservani, Rajesh K. Kesharwani, Nanobiomaterials, 2018
Recently, gene delivery scaffolds-based on DNA plasmid condensation with colloidal gold/cationic polymer was also developed via electrostatic interaction yielding gold/polyethyleneimine (PEI), gold/chitosan and gold/chitosan/PEI complexes. Luciferase-encoding plasmid DNA was subsequently added and adsorbed on the prepared scaffolds to be used as a non-viral gene delivery carrier. Confocal fluorescent microscopy was carried out to verify the presence of DNA in the cell using gold nano-scaffold as a carrier. Transfection efficiency assay using A549 and HeLa human cell lines was performed that reveal gold/polymer-based nano-scaffolds provided transfection efficiency approximately 10 times higher than polymeric-based gene carriers (Tencomnao et al., 2011; Nitta and Numata, 2013). Native glucagon like peptide 1 (GLP-1), an incretin hormone that regulates blood glucose level post-prandially, is used for the treatment of type 2 diabetes mellitus. In this study, to exploit the function of GLP-1, the glucosamine-based polymer chitosan was used as a cationic polymer-based in vitro delivery system for GLP-1, DPP-IV resistant GLP-1 analogues and siRNA targeting DPP-IV mRNA. It was reported that all chitosan–DPP-IV siRNA nanocomplexes were capable of DPP-IV silencing and carry out effective abrogating enzymatic activity of DPP-IV in media of silenced cells, and with no apparent cytotoxicity. These findings are lead to confirm the versatility of these specific formulations to deliver plasmid DNA and siRNA render their use as a combined in vivo therapy for the control of type 2 diabetes (Jean et al., 2012).
Closed-loop insulin delivery: update on the state of the field and emerging technologies
Published in Expert Review of Medical Devices, 2022
Other adjunctive therapies have been introduced to optimize glycemic control. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases satiety, slows gastric emptying and suppresses glucagon release. Initial small inpatient studies of GLP-1 use with fully closed-loop therapy seemed promising, but there have been no recent larger studies to evaluate outpatient efficacy [112]. Sodium-glucose co-transporter (SGLT2) inhibitors lower plasma glucose by blocking renal reabsorption and increasing renal excretion of glucose in an insulin-independent manner. Data on SGLT2 as an adjuvant in closed-loop therapy is limited, but results from a recent inpatient study in young adults using fully closed-loop with dapagliflozin were promising with no signs of hypoglycemia or ketosis [113]. Hybrid closed-loop with empagliflozin and simple meal announcement was non-inferior to hybrid closed-loop with carbohydrate counting (and no empagliflozin) in 30 adults on two days in another recent study [114]. Unfortunately, SGLT2s are no longer authorized for treatment of type 1 diabetes [115].
A dipyrrole derivative from Aloe vera inhibits an anti-diabetic drug target Dipeptidyl Peptidase (DPP)-IV in vitro
Published in Preparative Biochemistry & Biotechnology, 2020
C. Prasannaraja, A. S. Kamalanathan, M. A. Vijayalakshmi, Krishnan Venkataraman
Understanding the mechanism of pancreatic rejuvenation has increased considerably upon discovery of incretins such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which helps in maintaining glucose homeostasis (i.e., incretin effect) with increased β-cell mass and function.[5] GLP-1, is a glucose-dependent insulinotropic gut hormone, secreted by the intestinal L-cells that stimulate insulin secretion.[6] However, it is rapidly degraded by the ubiquitous proteolytic enzyme DPP-IV. Patients with type 2 diabetes have increased DPP-IV enzyme activity[7] and thus, inhibition of DPP-IV, the enzyme that makes GLP-1 biologically inactive, enhances the incretin effect and is considered as one of the targets for the treatment of T2DM.[8] Oral administration of synthetic DPP-IV inhibitors to type 2 diabetic patients effectively reduced glycated hemoglobin levels.[9] The synthetic DPP-IV inhibitors currently in use have very few side effects, however, the durability and long-term safety needs to be established.[10] Several food derived peptides and small molecules have been characterized for their anti-diabetic activity[11,12] and many of them have been identified and found to act as promising DPP-IV inhibitors, potentially contributing to glycemic control.[13–16]
Exenatide promotes the autophagic function in the diabetic hippocampus: a review
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Eman Mohammed Elsaeed, Ahmed Gamal Abdelghafour Hamad, Omnia S. Erfan, Mona A. El-Shahat, Fathy Abd Elghany Ebrahim
Exenatide is a synthetic anti-diabetic drug that modulates insulin release by enhancing glucose-dependent insulin secretion. It acts as a GLP-1 agonist, which is an incretin hormone, whose receptors are largely expressed throughout the body including the hippocampus. Exogenous GLP-1 administration is believed to restore blood glucose to near-normal levels, as diabetes is associated with the inactivation of the incretin system, which is thought to participate in the reduced regulation of insulin and glucagon secretion [6, 38].