A novel approach for noninvasive drug delivery and sensing through the amniotic sac

J Control Release. 2014 Jun 10:183:105-13. doi: 10.1016/j.jconrel.2014.03.040. Epub 2014 Mar 28.

Abstract

Current invasive prenatal tests (amniocentesis and chorionic villus sampling) are known for their risk to the fetus. In the last decade, the use and awareness of these prenatal tests have increased, resulting in growing demand for a safe, non-invasive, and accurate prenatal test. Chemical penetration enhancers (CPEs) have long been used to increase transport phenomena across skin and other membranes (e.g., tympanic membrane). The amniotic sac membrane is called the chorioamnion (CA) membrane and serves as the physical barrier between the fetus and the mother. In this research, the effect of CPEs on human CA mass transport was evaluated both in vitro and ex vivo. The results show that the tested CPEs exhibit an enhancing effect on CA mass transport. Based on the permeability results, two mechanisms of action were suggested: "extractors" and "fluidizers". Fourier transform infrared (FTIR) and rapid colorimetric screening measurements supported the mechanisms, based on which, more potent compounds were designed and tested for their enhancing effect. The enhancing mass transport effect of CPEs on CA membrane may be used both for sampling of cell-free DNA and for noninvasively administering drugs and other biological agents to the amniotic sac.

Keywords: Chemical penetration enhancers; Drug delivery and prenatal tests.

MeSH terms

  • Amnion / metabolism*
  • Amniotic Fluid / chemistry
  • Animals
  • Biological Transport
  • DNA / analysis
  • Dextrans / administration & dosage
  • Dextrans / chemistry
  • Dextrans / pharmacokinetics
  • Drug Delivery Systems / methods*
  • Female
  • Fluorescein-5-isothiocyanate / administration & dosage
  • Fluorescein-5-isothiocyanate / analogs & derivatives
  • Fluorescein-5-isothiocyanate / chemistry
  • Fluorescein-5-isothiocyanate / pharmacokinetics
  • Gestational Age
  • Humans
  • In Vitro Techniques
  • Permeability
  • Pharmaceutical Preparations / administration & dosage*
  • Pharmaceutical Preparations / chemistry*
  • Pharmaceutical Preparations / metabolism
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Rats, Sprague-Dawley
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Dextrans
  • Pharmaceutical Preparations
  • fluorescein isothiocyanate dextran
  • DNA
  • Fluorescein-5-isothiocyanate