title: A polypeptide drug carrier for maternal delivery and prevention of fetal exposure.
abstract: BACKGROUND
  Pregnant females are largely overlooked in drug development due to concerns for fetal health. Additionally, pregnancy is often an exclusion criterion in clinical trials, so the safety of many drugs during pregnancy is unknown.
  
  
  OBJECTIVE
  The goal of this study was to evaluate Elastin-like Polypeptide (ELP), a synthetic protein derived from human elastin, for maternally sequestered drug delivery. ELP is a versatile drug carrier with a long plasma half-life, low immunogenicity, and the ability to be fused to nearly any small molecule or protein-based therapeutic.
  
  
  METHODS
  We determined the pharmacokinetics, biodistribution, and fetal exposure to the ELP drug carrier using quantitative fluorescence techniques in a rat pregnancy model.
  
  
  RESULTS
  After either bolus IV administration or continuous infusion over five days, ELPs accumulated strongly in the kidneys, liver, and placenta, but importantly, little to no ELPs were detectable in the fetus. Within the placenta, ELPs were localized to the chorionic plate and broadly distributed within the labyrinth, but were excluded from the fetal portion of the chorionic villi.
  
  
  CONCLUSIONS
  These data indicate that ELP does not cross the placenta, and they suggest that this adaptable drug delivery system is a promising platform for prevention of fetal drug exposure.
authors.affiliation: Department of Physiology and Biophysics and.
authors.forename: Eric M
authors.initials: EM
authors.lastname: George
authors.forename: Huiling
authors.initials: H
authors.lastname: Liu
authors.forename: Grant G
authors.initials: GG
authors.lastname: Robinson
authors.forename: Gene L
authors.initials: GL
authors.lastname: Bidwell
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004549:Elastin / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008431:Maternal-Fetal Exchange; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D010455:Peptides; D004549:Elastin
keywords: Drug delivery; elastin-like polypeptide; fetal exclusion; placental transport; preeclampsia; pregnancy