SBIR Phase II: Dense Nanolipid Fluids (DNLFs) for Delivery of Drugs with Poor Bioavailability: Synthesis, Manufacture, and Drug Properties

The broader/commercial impact of this Small Business Innovation Research (SBIR) Phase II project would be the development of the first insulin pill for patients with diabetes. More than 800 million patients worldwide live with diabetes and the incidence is increasing. In the US, diabetes is the most expensive chronic disease that is aggravated by patients having an aversion to needles and skipping doses they cannot easily afford. Insulin pills sidestep the need for patients and caregivers to use syringes and needles and will address cost and supply chain issues that arise from the need to refrigerate injectable insulin products. Additionally, insulin pills can resolve therapeutic shortcomings of insulin injections including the potential for incorrect dosing and resultant complications like heart attacks, strokes, eye- and kidney disease. The technology supporting oral insulin is based on the continued development of lipid nanoparticles which promote safety by using lipids that are well known and tested and are approved as inert drug constituents or food additives. This research focuses on increasing the ability of lipid nanoparticles to encapsulate and promote the gastrointestinal absorption of insulin, and extending the shelf life of pills based on lipid nanoparticles. The proposed project addresses the high medical need for an oral insulin. Based on work supported by a phase I SBIR award that demonstrated the concept of encapsulating insulin in lipid nanoparticles, an insulin pill will be developed. Because taking insulin by mouth will more closely mimic natural insulin production than subcutaneous injections, the body’s natural processes to balance blood glucose levels should be more engaged. If these processes were fully engaged, the requirement for glucose monitoring would be eliminated and insulin overdosing, a common problem from subcutaneous injection, would be prevented. However, how much oral insulin dosing will enable natural glucose and insulin control can only be known once an effective oral dosage form is available. By providing an insulin pill made by encapsulating insulin in lipid nanoparticles, and optimizing the ability of lipid nanoparticles to move insulin from the gastrointestinal tract into the body, our research will open up new opportunities to understand human glucose metabolic processes. Our research will also contribute basic, general knowledge about nanoparticle manufacturing, optimization and oral absorption that will close a technology gap in developing oral drugs based on peptides including insulin, vaccines, and GLP-1 drugs as well as other non-peptide drugs. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.