Advances in micro- and nanotechnologies for the GLP-1-based therapy and imaging of pancreatic beta-cells

Abstract

Therapies to prevent diabetes in particular the progressive loss of β-cell mass and function and/or to improve the dysregulated metabolism associated with diabetes are highly sought. The incretin-based therapy comprising GLP-1R agonists and DPP-4 inhibitors have represented a major focus of pharmaceutical R&D over the last decade. The incretin hormone GLP-1 has powerful antihyperglycemic effect through direct stimulation of insulin biosynthesis and secretion within the β-cells; it normalizes β-cell sensitivity to glucose, has an antiapoptotic role, stimulates β-cell proliferation and differentiation, and inhibits glucagon secretion. However, native GLP-1 therapy is inappropriate due to the rapid post-secretory inactivation by DPP-4. Therefore, incretin mimetics developed on the backbone of the GLP-1 or exendin-4 molecule have been developed to behave as GLP-1R agonists but to display improved stability and clinical efficacy. New formulations of incretins and their analogs based on micro- and nanomaterials (i.e., PEG, PLGA, chitosan, liposomes and silica) and innovative encapsulation strategies have emerged to achieve a better stability of the incretin, to improve its pharmacokinetic profile, to lower the administration frequency or to allow another administration route and to display fewer adverse effects. An important advantage of these formulations is that they can also be used at the targeted non-invasive imaging of the beta-cell mass. This review therefore focuses on the current state of these efforts as the next step in the therapeutic evolution of this class of antidiabetic drugs.

The Impact of Natural and Synthetic Polymers in Formulating Micro and Nanoparticles for Anti-Diabetic Drugs

“…Poly (d,l-lactic-co-glycolic acid)(PLGA) has been widely used as a therapeutic drug delivery system in protein or polypeptide formulations due to its good biocompatibility and biodegradability [5,16,17,18,19]. This polymer consists of various ratios of lactic acid and glycolic acid [8,18,20]. The degradation properties of PLGA can be controlled by changing the ratio between lactic acid and glycolic acid [20].…”

“…Therefore, in order to increase half-life the polymer based sustained release formulation of exenatide was developed using PLGA which is now marketed as Bydureon® by Astra Zeneca. Bydureon® is a long acting GLP-1R agonist that is administered subcutaneously once a week [17,18,19]. The Bydureon® PLGA microspheres (60 µm in diameters) were prepared by water-in-oil solvent evaporation method [12,19].…”

Extra-oral bitter taste receptors: New targets against obesity?

“…It is an important incretin that decreases blood glucose levels by stimulating insulin release. GLP-1 mimetics are currently used for the treatment of obesity-related type 2 diabetes [42]. PYY is also released from L-cells in the distal gut in response to feeding to reduce appetite.…”

Novel strategies to oral delivery of insulin: Current progress of nanocarriers for diabetes management

“…Oral, nasal, pulmonary, rectal, and transdermal alternative drug delivery systems (DDS) have been previously investigated for insulin delivery (Easa et al, 2019; Shah et al, 2016). Of these, oral delivery is a non‐invasive, safe, and convenient route that could mimic the physiological behavior of endogenous insulin (Moonschi et al, 2018); however, major obstacles remain, including rapid enzymatic degradation of insulin in the stomach and intestinal lumen, low bioavailability due to its large size, the absence of lipophilicity, and poor permeability across the intestinal epithelium (Liu et al, 2018). Furthermore, drug delivery systems (DDS) and their derivatives have been developed based on chemical and morphological modifications, all of which promoted delivery and therapy efficiency (Tong et al, 2020).…”