|M.Sc Student||Salzmann Nir Izhak|
|Subject||Development of a Dry System for Oral Delivery of Insulin|
|Department||Department of Biotechnology and Food Engineering||Supervisor||Dr. Eyal Shimoni|
|Full Thesis text|
Advances in recombinant DNA technology and progress in biotechnology paved the way for the mass scale production of therapeutic proteins and peptides without the shortcomings of animal-derived products such as viral contamination or immunogenicity. These therapeutic proteins often need careful attention in their handling, storage and administration compared with conventional low-molecular-weight drugs routinely processed in the pharmaceutical industry. Additionally there are many hurdles that have to be overcome in the delivery of peptide and protein drugs. Since their bioavailability is poor when administered non-parenterally, traditional forms of administration rely on their parenteral injection. Parenteral application include intravenous, intramuscular or subcutaneous administration using a syringe and needle, which most often is inconvenient for the patient, and may cause patients to comply less to their given treatment. As a consequence, several alternative routes of protein drug delivery have been developed with the aim of eliminating the pain, inconvenience and disruption of lifestyle associated with the need for daily injections.
The major barriers to developing a desirable oral formulation for peptides and proteins are digestive enzymes, which degrade proteins in the gastro-intestinal tract before they can be absorbed. Impermeable mucosal tissues in the intestine also inhibit the protein reaching the bloodstream. In this work we showed the capability to produce a dry enteral insulin drug based on insulin, protease inhibitor and penetration enhancer. The first task was to produce insulin microcapsules which maintain biological activity at room temperature. Cell based method was used to measure the bioactivity of insulin using an insulin dependent LB cell line. This method allowed us to examine the spray freeze manufacturing parameters, determining the optimal encapsulation matrix for better insulin activity. The technique was also to produce microcapsules containing protease inhibitor and penetration enhancer. The second phase of this work focused on testing the developed insulin formula in model animals. The results show that insulin maintained its biological activity, and also demonstrated the possibility to deliver bioactive insulin through the lumen mucosa into the portal vein, to mimic the natural path of insulin secretion. The insulin formula had a positive effect of lowering the blood glucose level.