Emerging Strategies to Improve the Stability and Bioavailability of Insulin: An Update on Formulations and Delivery Approaches.

One of the primary goals of diabetes management is to maintain blood glucose levels within a normal range, and insulin plays a vital role in achieving this. All Type 1 DM patients and advanced Type 2 DM patients require insulin. Insulin is administered subcutaneously, which may cause patient discomfort from the use of needles. Therefore, developing alternative routes of insulin administration has always been a major focus of diabetes research. This review aims to provide an update on the insulin formulations and delivery routes as well as strategies used to improve its stability and bioavailability for the treatment of diabetes.

Role of surface-exposed charged basic amino acids (Lys, Arg) and guanidination in insulin on the interaction and stability of insulin-insulin receptor complex.

Naturally occurring proteins are emerging as novel therapeutics in the protein-based biopharmaceutical industry for the treatment of diabetes and obesity. However, proteins are not suitable for oral delivery due to short half-life, reduced physical and chemical stability and low permeability across the membrane. Chemical modification has been identified as a formulation strategy to enhance the stability and bioavailability of protein drugs. The present study aims to study the effect of charge-specific modification of basic amino acids (Lys, Arg) and guanidination on the interaction of insulin with its receptor using molecular modelling. Our investigation revealed that the guanidination of insulin (Lys-NHC = NHNH2) enhanced and exerted stronger binding of the protein to its receptor through electrostatic interaction than native insulin (Lys-NH3+). Point mutations of Lys and Arg (R22, K29; R22K, K29; R22, K29R; R22K, K29R) were attempted and the effects on the interaction and stability between insulin/modified insulins and insulin receptor were also analyzed in this study. The findings from the study are expected to provide a better understanding of the possible mechanism of action of the modified protein at a molecular level before advancing to real experiments.