Formulation Development of Probiotics for Women's and Neonatal Health Applications in Developing Countries

Several probiotic bacterial strains have been identified as critical players in healthy neonatal development and in maintaining a healthy vaginal microbiome in women. Specifically, it has been observed that infants with low numbers of Bifidobacterium infantis are at higher risk for developing premature birth complications, allergy disorders, and reduced weight gain. Further, it has been documented that women with low numbers of Lactobacillus crispatus in the vaginal microbiome are at higher risk for contracting a variety of microbial and viral vaginal infections, and are at risk for reduced fertility. There are many challenges associated with administration of these probiotics to the infant gut or to the vaginal tract as these probiotics suffer from high sensitivity to oxygen and harsh environmental conditions. This makes these probiotics difficult to formulate, transport, and administer to patients while maintaining their viability. Here, we use high-throughput excipient library screening, formulation development, in vivo pharmacokinetic characterization in sheep (vaginal delivery) and swine (oral delivery), and microbiome analysis to develop highly stable formulations of these probiotics. We explore how lyophilization, prolonged heat exposure, and moisture affect the viability of these probiotics within our formulations. We further characterize how the various physiochemical properties of our formulations impact the in vitro release kinetics and the in vivo probiotic pharmacokinetics following oral or vaginal delivery. Overall, this work gleans insights into how formulation development strategies can improve the potential for successful administration of highly sensitive probiotic microbes to support healthy neonatal development and to protect women's vaginal and reproductive health.