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

Abstract

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.

Alginate Nanoformulation: Influence of Process and Selected Variables

“…Another study was conducted to evaluate the particle size of insulin nanoparticles synthesized via emulsification/internal gelation. Similar trend of results was observed where the reduction of particle size (442 nm to 317 nm) was enabled by applying ultrasonication for 15 min, after which the size started to expand [ 161 ]. To enable a marked reduction of particle size, it was envisaged that ultrasound sonication brought about emulsion droplet breakdown by means of cavitation phenomena, yet lengthening this process time rendered the coalescence of emulsion droplets as a result of elevating the medium temperature and hence larger particle size [ 162 ].…”

“…As shown in Table 6 , alginate-chitosan nanoparticles with small size and high encapsulation efficiency were produced at halfway between pKa of these species (pH ~ 4.8). Besides, intensifying of electrostatic interactions is represented by zeta potential values, in which high negative values indicate an absence of free cationic groups on the surface of nanoparticles, that correlated to high encapsulation efficiency and drug loading propensity [ 161 ].…”

Chitosan/Albumin Coating Factorial Optimization of Alginate/Dextran Sulfate Cores for Oral Delivery of Insulin

“…This three-hour insulin release would result in its availability close to the absorption site, which constitutes an excellent benefit for oral insulin bioavailability [ 19 ]. CD, the technique to monitor the integrity of insulin against harsh conditions [ 18 ], as seen in Figure 1 , showed that the spectrum of unprocessed standard insulin (I) in PBS at pH 7.4 has bands with two minima at approximately 209 and 224 nm, indicating the presence of a significant α-helix structure with some β–sheets. Insulin released from nanoparticles (II) showed a similar spectrum.…”

“…Chitosan stabilizes alginate-based hydrogels during the formulation of nanoparticles and enhances insulin absorption through the paracellular route [ 17 ]. Chitosan coating is essential to strengthen the alginate/dextran sulfate core [ 18 ] and to incorporate other polyanionic biopolymers that increase insulin stability against GI enzymes and pH and to modulate insulin release in the GI tract [ 19 , 20 ].…”

Developments in encapsulation of insulin: Is oral delivery now possible?

“…However, it does not mean that this tech-nology is perfect, since it may cause some consumer feel nausea. Thus, if researchers want to use this technology as food application, some specific corrigent is necessary [49][50][51][52][53][54][55] .…”