Hypoglycemic Effect of Orally Delivered Insulin Nanoparticles Compared to Subcutaneous Recombinant Human Soluble Insulin in Hyperglycemic Male Rats

Abstract

Background: Insulin is available as an injectable drug and remains the mainstay of therapy. Researchers have attempted to develop an oral formulation of insulin, particularly utilizing nanoparticles (NPs). Objective: To assess the efficacy and safety of insulin-loaded D-α-Tocopherol polyethylene glycol succinate (TPGS)-emulsified PEG-capped PLGA NP in comparison to insulin-loaded PLGA NP and subcutaneous (SC) insulin in an in vitro and in vivo diabetic rat model. Methods: Two biocompatible and biodegradable NPs were used, in which 20 IU/kg of recombinant human soluble insulin was incorporated. NP1 was PLGA-loaded with human insulin, while NP2 was PLGA-PEG-TPGS-loaded with human insulin. The physical characteristics of the NPs were examined in an in vitro and in vivo study on a hyperglycemic rat model for a 24-hour duration. Results: For the first 3 hours, SC insulin showed a better reduction in serum glucose levels (SG) compared to both NP1 and NP2. A smooth, sustained reduction in SG was observed and maintained till the end of 24 hours with both NPs. NP1 maintained SG reduction for 6 hours before experiencing an increase, while NP2 demonstrated superior sustained reduction in SG beyond the 12-hour evaluation period. Conclusions: PLGA-PEG-TPGS NP can act as a potential carrier for oral insulin delivery and maintain good glycemic control for up to 24 hours.