Oral delivery of insulin for diabetes therapy: Development and evaluation of insulin loaded polymer/lipid based carrier systems

Diabetes is a chronic metabolic disorder that affects nearly 500 million people worldwide. Its hallmark feature, hyperglycaemia is caused due to insulin deficiency and/or resistance. Poor patient compliance of subcutaneous insulin injections warrants development of a formulation for alternative non-¬invasive administration. The current study aims to develop a polymer/lipid based carrier system for oral delivery of insulin. Specific objectives of this study include formulation of polymer/lipid based micro/nanoparticles followed by a critical evaluation of their characteristics i.e. particle size, surface properties, loading ¬efficiency, computational modelling of molecular interactions etc. Evaluation of the release profile of insulin following the loading of micro/nanoparticles into enteric¬ coated gelatin capsules; their protection efficiency in simulated¬ gastrointestinal media would also be carried out. Morphological analysis of the micro/nanoparticles using electron microscopy, evaluation of the toxicity of these formulations and permeation of insulin across epithelial cell monolayer (e.g. Caco¬2 cells) would be undertaken. The in vivo hypoglycaemic activity of formulated insulin would also be investigated following its administration via oral route using a rat model. It is anticipated, based on the previous evidence, that the micro/nanoparticulate system once released from the capsule would enhance insulin absorption through the intestinal barrier, presumably by opening up the epithelial tight -junctions thus enhancing insulin bioavailability.

This project entails mastering of a variety of analytical techniques by the student during the course of the project which include HPLC, LC¬MS (liquid chromatography coupled with a mass spectrophotometer), NMR (nuclear magnetic resonance spectroscopy), ELISA (Enzyme ¬linked immunosorbent Assay), molecular modelling, cell culture techniques to name a few. The supervisory team brings in a range of expertise into the project which gives a multi-disciplinary approach to the project.