Platform technology for delivery of stabilized therapeutic microbes in powders with high water activity

/Abstract (NEC) in preterm infants affects 0.3-2.4 infants per 1,000 live births in the US and is a leading cause of mortality (mortality rate of up to 45%) and morbidity in premature babies. Although the pathogenesis of the disease is not fully understood, an abnormal gut microbiome, e.g., dysbiosis, has been recognized as a critical determinant in NEC. Multiple clinical trials investigating microbial treatments for NEC report upwards of 50% reduction in NEC occurrence in infants, leading to the use of probiotic for prevention NEC in preterm infants. Importantly, whole gut transit times between adults and newborns are vastly different (35 hours vs 8.5 hours, respectively) which leads to rising variability and challenges in proving effectiveness when microbes typically given to adults are dosed to preterm infants. Unfortunately, the variability in dose, microbial strain, delivery method, and viability lead to inconsistent results, ineffective treatments, and consequently, pediatricians are reluctant to prescribe probiotic for prevention of NEC. There is an urgent need for high-quality probiotic products to fulfill nutritional needs of preterm infants, that are developed following rigorous scientific and manufacturing standards; and provide accurate, reproducible, and effective dose following administration. A patented platform encapsulation technology for the protection of next-generation microbial medicines has been developed. The gastric survival of Lactobacillus rhamnosus HN001 (HN001) and Bifidobacterium animalis subsp. Lactis HN019 (HN019) has been increased, resulting in a greater than 1-million-fold increase in viable count following 1 hr exposure to simulated gastric fluid. Further, HN001 encapsulated in VitaKey’s proprietary formulation exhibited 0-log loss in viability over 4 weeks in high water activity milk powder at 25°C, 30°C, and 35°C, while control bacteria (i.e. HN001) experienced 0.41, 0.91, and 1.3 log-loss in viability at the same temperatures, respectively. This proposal aims to expand the coating technology to use materials which are approved for use in infant formula powder to develop the world’s first probiotic specifically designed for the unique GI tract of neonates. Multiple excipients will be examined in the formulation by evaluating gastric stability, targeted intestinal release, maintenance of stable/viable microbes, and shelf stability. This project aims to develop formulations with probiotic species which have been reported to reduce occurrence of NEC. Project Number: 1R43HD117653-01 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Aaron Anselmo | Institution: VITAKEY, INC., WASHINGTON, DC | Award Amount: $349,759 | Activity Code: R43 | Study Section: Special Emphasis Panel[ZRG1 EMS-S (10)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R43HD11765301