Pulmonary administration of cross-linked chitosan nanoparticles of genistein for regulating blood glucose.

The research study focused on the development and characterization of sustained release formulation of genistein (GEN)-loaded chitosan (CS) nanoparticles to deliver in the form of dry powder inhaler (DPI) via pulmonary route to offer higher stability and anti-diabetic activity. The GEN-loaded nanoparticles were prepared by cross-linking reaction of CS and sodium hexametaphosphate (SHMP). The optimized formulation displayed particle size (PS) of 684.2 ± 26.5 nm, zeta potential (ZP) of 19.6 ± 4.50 mV, % entrapment efficiency (% EE) of 87.33 ± 8.46 % and drug release profile of 85.48 ± 5.50 % for 48 h. The in-vivo studies exhibited a superior sustained release formulation of GEN in the regulation of blood glucose levels (BGLs). The powder showed the emitted fraction (EF) of 86.76 % and effective inhalation index (EI) of 85.41 %. The reduction of BGLs (85 %) was observed in the diabetic group. This might be due to the inhibition of proliferation of pancreatic ß-cells (growth factor inhibition targeting cAMP and ERK1/2 pathway), antioxidative activity, reducing insulin resistance, and the adipose tissue mass and alteration of the hepatic glucose metabolism. Hence, these results proved the delivery of GEN in the form of DPI system as a favorable route for treating type-1 diabetes mellitus with a longer duration of action.

Strategies for the delivery of antidiabetic drugs via intranasal route.

Diabetes is a metabolic disorder defined by higher blood glucose levels in the body generally controlled by antidiabetic agents (oral) and insulin (subcutaneous). To avoid the limitations of the conventional routes such as lower bioavailability and pain at the site of injection in case of parenteral route modified delivery systems are proposed like transdermal, pulmonary and inhalation delivery and among the other delivery systems nasal drug delivery system that shows the advantages such as reduced frequency of dose, higher patient compliance, safety, ease of administration, prolonged residence time, improved absorption of drug in the body, higher bioavailability and stability. This review article discusses the strategies adopted for the delivery of antidiabetic drugs by the intranasal delivery system. The insulin and glucagon-like peptides on experimentation show results of improved therapeutic levels and patient compliance. The drugs are transported by the paracellular route and absorbed through the epithelial tight junctions successfully by utilising different strategies. The limitations of the nasal delivery such as irritation or burning on administration, degradation by the enzymes, mucociliary clearance, lesser volume of the nasal cavity and permeation through the nasal mucosa. To overcome the challenges different strategies for the nasal administration are studied such as polymers, particulate delivery systems, complexation with peptides and smart delivery using glucose-responsive systems. A vast scope of intranasal preparations exists for antidiabetic drugs in the future for the management of diabetes and more clinical studies are the requirement for the societal impact to battle against diabetes.