title: A novel approach for noninvasive drug delivery and sensing through the amniotic sac.
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.
authors.affiliation: Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Aharon
authors.initials: A
authors.lastname: Azagury
authors.affiliation: Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Eliz
authors.initials: E
authors.lastname: Amar-Lewis
authors.affiliation: Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Mann
authors.affiliation: Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Riki
authors.initials: R
authors.lastname: Goldbart
authors.affiliation: Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Traitel
authors.affiliation: Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Raz
authors.initials: R
authors.lastname: Jelinek
authors.affiliation: Departments of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel.
authors.forename: Mordechai
authors.initials: M
authors.lastname: Hallak
authors.affiliation: Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: kost@bgu.ac.il.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kost
mesh_terms: D000650:Amnion / Q000378:metabolism*; D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D001692:Biological Transport; D004247:DNA / Q000032:analysis; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D005865:Gestational Age; D006801:Humans; D066298:In Vitro Techniques; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D003911:Dextrans; D004364:Pharmaceutical Preparations; C015219:fluorescein isothiocyanate dextran; D004247:DNA; D016650:Fluorescein-5-isothiocyanate
keywords: Chemical penetration enhancers; Drug delivery and prenatal tests