Abstract
Preterm birth (PTB) is a major cause of infant mortality in the United States and around the globe. Makena®—once-a-week intramuscular injection of 17-α Hydroxyprogesterone caproate (17P)—is the only FDA approved treatment for the prevention of PTB. Invasive delivery of 17P requires hospitalization and expert personnel for injection. Vaginal delivery of 17P would be preferable, because of high patient compliance, reduced systemic exposure, fewer side effects, and no need for hospitalization. The objective of the present study was to prepare and evaluate a self-nanoemulsifying vaginal tablet of 17P. A solid self-nanoemulsifying preconcentrate (S-SNEDDS) of 17P and dimethylacetamide (DMA) was developed using medium chain triglycerides, a non- immunogenic surfactant, and co-processed excipient (PVA-F100). The tablet prepared was characterized for emulsification time, particle size, solid state properties, and drug release. The formulation showed >50% inhibition of TNF-α release from LPS-stimulated RAW 264.7 cells. Importantly, there were significant differences in rates of PTB and average time to delivery between control and vaginal 17P-treated groups in LPS-stimulated timed pregnant E15.5 mice. Considering the lacuna of therapeutic approaches in this area, vaginal delivery of 17P for the prevention of preterm birth has significant clinical relevance.
Highlights
Prematurity is the leading cause of infant death and the second-leading cause of childhood death before the age of 5 [1]
Risks of preterm birth and infant mortality are higher for black infants born to mothers residing in the most segregated cities and neighborhoods, and there is a positive correlation between preterm delivery and lower household income and medicaid eligibility
The main objective of this paper is to develop and characterize a 17-alpha hydroxyprogesterone caproate (17P)-loaded vaginal tablet and evaluate in vivo efficacy using a mouse model of preterm birth
Summary
Prematurity is the leading cause of infant death and the second-leading cause of childhood death before the age of 5 [1]. African-American/non-Hispanic black infants disproportionately bear the burden of extreme prematurity (
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