Probing insulin bioactivity in oral nanoparticles produced by ultrasonication-assisted emulsification/internal gelation.

Alginate-dextran sulfate-based particles obtained by emulsification/internal gelation technology can be considered suitable carriers for oral insulin delivery. A rational study focused on the emulsification and particle recovery steps was developed in order to reduce particles to the nanosize range while keeping insulin bioactivity. There was a decrease in size when ultrasonication was used during emulsification, which was more pronounced when a cosurfactant was added. Ultrasonication add-on after particle recovery decreased aggregation and led to a narrower nanoscale particle-size distribution. Insulin encapsulation efficiency was 99.3%±0.5%, attributed to the strong pH-stabilizing electrostatic effect between insulin and nanoparticle matrix polymers. Interactions between these polymers and insulin were predicted using molecular modeling studies through quantum mechanics calculations that allowed for prediction of the interaction model. In vitro release studies indicated well-preserved integrity of nanoparticles in simulated gastric fluid. Circular dichroism spectroscopy proved conformational stability of insulin and Fourier transform infrared spectroscopy technique showed rearrangements of insulin structure during processing. Moreover, in vivo biological activity in diabetic rats revealed no statistical difference when compared to nonencapsulated insulin, demonstrating retention of insulin activity. Our results demonstrate that alginate-dextran sulfate-based nanoparticles efficiently stabilize the loaded protein structure, presenting good physical properties for oral delivery of insulin.

Intestinal uptake of insulin nanoparticles: facts or myths?

The oral route is the most suitable and physiological delivery route. Oral insulin delivery would minimize the health hazard implied in repeated injection, surpass complications arising from the need for sterile techniques associated with parenteral formulations and provide better glucose homeostasis. However, it is limited by various physiological barriers and still remains a scientific challenge. The desire to deliver insulin by the oral route in a conveniently and effectively way has led to the intense investigation of new delivery systems. Nanodelivery systems have been proposed to enhance the bioavailability of insulin after oral administration. This review article describes the gastrointestinal barriers to oral insulin delivery, including chemical, enzymatic and absorption barriers. The potential transport mechanisms of insulin delivered by nanoparticles across the intestinal epithelium are also addressed. Finally, how nanoparticles characteristics affect insulin pharmacological activity and bioavailability is discussed.