STTR Phase II: Developing a novel drug delivery system to enable an oral peptide-based drug for kidney stones

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The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase II project is a novel drug delivery system composed of peptide-loaded nanoparticles (NPs) for targeted and sustained release of therapeutic peptides to the intestine. The drug resulting from this project will be first-in-class comprehensive treatment for hyperoxaluria (high urine oxalate), hyperoxalemia (high blood oxalate), and related calcium oxalate kidney stones (COKS). Millions of patients suffering from COKS will finally be able to prevent this painful and damaging disease and preserve their long-term kidney health. Since a single kidney stone increases the risk of kidney failure, payers will not only appreciate the annual savings on treatment, but also the economic benefits of preventing chronic kidney disease (CKD) and kidney failure requiring permanent dialysis, affecting ~45 M and ~500 K patients in the US, respectively. Importantly, it will also impact the outcome of other disorders potentially affected by oxalate, including CKD and its progression, progression of cyst growth in autosomal dominant polycystic kidney disease, kidney disease-associated cardiovascular diseases, and poor renal transplant survival. This STTR Phase II project aims to develop the oral route component of an innovative drug delivery system using peptide-loaded NPs for localized and sustained delivery of novel therapeutic peptides to the intestinal mucosa to address oxalate-related disorders. This project will: (1) Develop and characterize multiple NPs formulations. (2) Ensure that the peptide-loaded NPs are largely delivered to the small and large intestines, but not to the stomach. (3) Confirm that the NPs have no cellular toxicity in vitro. (4) Confirm that NPs significantly reduce plasma and urinary oxalate levels in hyperoxalemia and hyperoxaluric mice without causing significant in vivo toxicity, and achieving no or minimal systemic absorption. (5) Obtain initial safety data for the peptide-loaded NP via an exploratory preclinical toxicology study. At least one of the developed NP formulations should deliver the peptides to the small and large intestines, present no significant cellular toxicity in vitro, and reduce plasma and urinary oxalate levels without causing significant in vivo toxicity.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.