A vaginal nanoformulation of a SphK inhibitor attenuates lipopolysaccharide-induced preterm birth in mice

Nanomedicine (Lond). 2019 Nov;14(21):2835-2851. doi: 10.2217/nnm-2019-0243. Epub 2019 Nov 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Availability
  • Drug Compounding
  • Drug Liberation
  • Drug Stability
  • Emulsions / chemistry*
  • Emulsions / pharmacology
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Lipopolysaccharides / metabolism*
  • Male
  • Mice
  • Nanocapsules / chemistry*
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
  • Pregnancy
  • Premature Birth / drug therapy*
  • Solubility
  • Vagina

Substances

  • Emulsions
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Nanocapsules
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase