Oral Insulin Delivery Using Deoxycholic Acid Conjugated PEGylated Polyhydroxybutyrate Co-polymeric Nanoparticles

Aim: To develop insulin loaded deoxycholic acid conjugated PEGylated polyhydroxybutyrate co-polymeric nanoparticles and carry out in vitro and in vivo testing of enteric coated granules comprising these nanoparticles.

Materials & Methods: Insulin loaded nanoparticles were prepared and characterized in vitro. Cellular uptake was studied using hyperspectral and live cell confocal microscopy. Enteric coated granules of nanoparticles were fed orally to diabetic rats and the pharmacokinetic and pharmacodynamic parameters were evaluated.

Results: Ultra small (˜10 nm) nanoparticles with polydispersity index of 0.299 were obtained. The enteric coated granules showed a negligible insulin release in acidic pH, but released insulin in alkaline environment. High cellular uptake was observed and nanoparticles were able to maintain the blood glucose levels up to 24 h.

Conclusion: These enteric-coated nanoparticle granules sustained the release of insulin and showed enhanced insulin bioavailability. Hence, these may serve as a platform device for oral insulin delivery with extended release.