STTR Phase I: Sustained Delivery of Peptides with Inverse Flash Nanoprecipitation

This STTR Phase I project aims to pioneer a novel approach for the sustained delivery of peptide therapeutics using nano-composite microparticles. Peptide therapeutics tend to suffer from rapid enzymatic degradation and clearance, with half-lives on the order of minutes, and require frequent injections. The goal of a sustained release formulation is to reduce the frequency of injections by slowly releasing the therapeutic over a period of weeks to months. This will result in improved patient compliance and quality of life. Patient non-compliance is an economic burden that is estimated to cost the healthcare system over $100 billion/year. The lack of commercial success of existing sustained release technologies is due to low loading efficiencies, lack of controlled release at higher loading, and complex manufacturing. These limitations can be overcome with the newly-developed inverse Flash NanoPrecipitation (iFNP) process to produce nano-composite microparticles. This project aims to develop and test a once-monthly injectable formulation of a peptide therapeutic for type 2 diabetes that is currently injected daily. This research will aid in the understanding of the fundamental materials science and engineering principles that control therapeutic release from nano-composite microparticles. The rules for controlling release will apply broadly to other peptides, and this research will help to more rapidly develop future long-acting formulations. Current methods to produce peptide-loaded microparticles suffer from low drug loadings and poor encapsulation efficiencies, two of the most important factors for commercial viability. In contrast to existing methods, the iFNP technology allows for the assembly of nanoparticles with peptide loadings greater than 50wt% and encapsulation efficiencies greater than 90% in a fully scalable process. The nanoparticles are then assembled into microparticles to create the final sustained release formulation. Each drug-containing pore inside the microparticle is surrounded by a dense hydrophobic polymer layer which allows for therapeutic loadings 10x higher than competing technologies. The iFNP process has been demonstrated on a number of proof-of-concept molecules. In this project, iFNP will be used to produce a formulation of a peptide for diabetes therapy with a month-long release profile. The first goal of this project is to develop an understanding of the physical parameters that control the peptide stability and release. Supporting this goal, the peptide will be formulated with polymers of varying glass transition temperatures and degradation rates, and the release profiles will be measured in vitro. The efficacy of the optimal in vitro formulation will then be tested in a rat model. These studies are an important step in developing a commercial product that can positively impact patient care. 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.