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. PURPOSE: 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. CONCLUSION: 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.
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. PURPOSE: The goal of this study was to evaluate Elastin-like Polypeptide (ELP), a synthetic protein derived from humanelastin, 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. CONCLUSION: 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: C Rousselle; M Smirnova; P Clair; J M Lefauconnier; A Chavanieu; B Calas; J M Scherrmann; J Temsamani Journal: J Pharmacol Exp Ther Date: 2001-01 Impact factor: 4.030
Authors: Wenge Liu; Jonathan McDaniel; Xinghai Li; Daisuke Asai; Felipe Garcia Quiroz; Jeffery Schaal; Ji Sun Park; Michael Zalutsky; Ashutosh Chilkoti Journal: Cancer Res Date: 2012-11-15 Impact factor: 12.701
Authors: Eric M George; Fakhri Mahdi; Omar C Logue; Grant G Robinson; Gene L Bidwell Journal: J Ocul Pharmacol Ther Date: 2015-12-16 Impact factor: 2.671
Authors: John V Ilekis; Ekaterini Tsilou; Susan Fisher; Vikki M Abrahams; Michael J Soares; James C Cross; Stacy Zamudio; Nicholas P Illsley; Leslie Myatt; Christine Colvis; Maged M Costantine; David M Haas; Yoel Sadovsky; Carl Weiner; Erik Rytting; Gene Bidwell Journal: Am J Obstet Gynecol Date: 2016-03-10 Impact factor: 8.661
Authors: Adrian C Eddy; John Aaron Howell; Heather Chapman; Erin Taylor; Fakhri Mahdi; Eric M George; Gene L Bidwell Journal: Hypertension Date: 2019-12-02 Impact factor: 10.190
Authors: Alejandro R Chade; Nathan A Tullos; Taylor W Harvey; Fakhri Mahdi; Gene L Bidwell Journal: J Am Soc Nephrol Date: 2015-11-05 Impact factor: 10.121