Aim: Previously, we have shown that inhibition of SphK by the SphK inhibitor-II (SKI II) prevents lipopolysaccharide-induced preterm birth in mice. The aim of this study was to develop a vaginal self-nanoemulsifying drug-delivery system (SNEDDS) for SKI II. Materials & methods: A SKI II-loaded SNEDDS was characterized and tested in a murine preterm birth model. Results: The SNEDDS immediately formed a gel and then slowly emulsified to nanoglobules with over 500-fold enhancement of SKI II solubility at vaginal pH. Intravaginal administration of the SKI II SNEDDS significantly decreased lipopolysaccharide-induced preterm birth in mice. Conclusion: A vaginal nanoformulation of SKI II represents a novel, noninvasive approach to prevent preterm birth.
Keywords: SKI II; SNEDDS; inflammation; lipopolysaccharide; nanoformulation; preterm birth; sphingosine kinase inhibitor; vaginal administration.