Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction

Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus resulting from sys...

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Autores principales:	Lewis J. Renshall, Frances Beards, Angelos Evangelinos, Susan L. Greenwood, Paul Brownbill, Adam Stevens, Colin P. Sibley, John D. Aplin, Edward D. Johnstone, Tambet Teesalu, Lynda K. Harris
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	placenta pregnancy fetal growth restriction liposomes epidermal growth factor Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/31d09fe8761e42b3bf935d5bee54fcfc
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spelling	oai:doaj.org-article:31d09fe8761e42b3bf935d5bee54fcfc2021-11-25T18:40:37ZTargeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction10.3390/pharmaceutics131117781999-4923https://doaj.org/article/31d09fe8761e42b3bf935d5bee54fcfc2021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1778https://doaj.org/toc/1999-4923Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus resulting from systemic drug delivery. The use of targeted liposomes to selectively deliver payloads to the placenta has the potential to overcome these issues. In this study, we assessed the safety and efficacy of epidermal growth factor (EGF)-loaded, peptide-decorated liposomes to improve different aspects of placental function, using tissue from healthy control pregnancies at term, and pregnancies complicated by FGR. Phage screening identified a peptide sequence, CGPSARAPC (GPS), which selectively homed to mouse placentas in vivo, and bound to the outer syncytiotrophoblast layer of human placental explants ex vivo. GPS-decorated liposomes were prepared containing PBS or EGF (50–100 ng/mL), and placental explants were cultured with liposomes for up to 48 h. Undecorated and GPS-decorated liposomes containing PBS did not affect the basal rate of amino acid transport, human chorionic gonadotropin (hCG) release or cell turnover in placental explants from healthy controls. GPS-decorated liposomes containing EGF significantly increased amino acid transporter activity in healthy control explants, but not in placental explants from women with FGR. hCG secretion and cell turnover were unaffected by EGF delivery; however, differential activation of downstream protein kinases was observed when EGF was delivered via GPS-decorated vs. undecorated liposomes. These data indicate that targeted liposomes represent a safe and useful tool for the development of new therapies for placental dysfunction, recapitulating the effects of free EGF.Lewis J. RenshallFrances BeardsAngelos EvangelinosSusan L. GreenwoodPaul BrownbillAdam StevensColin P. SibleyJohn D. AplinEdward D. JohnstoneTambet TeesaluLynda K. HarrisMDPI AGarticleplacentapregnancyfetal growth restrictionliposomesepidermal growth factorPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1778, p 1778 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	placenta pregnancy fetal growth restriction liposomes epidermal growth factor Pharmacy and materia medica RS1-441
spellingShingle	placenta pregnancy fetal growth restriction liposomes epidermal growth factor Pharmacy and materia medica RS1-441 Lewis J. Renshall Frances Beards Angelos Evangelinos Susan L. Greenwood Paul Brownbill Adam Stevens Colin P. Sibley John D. Aplin Edward D. Johnstone Tambet Teesalu Lynda K. Harris Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction
description	Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus resulting from systemic drug delivery. The use of targeted liposomes to selectively deliver payloads to the placenta has the potential to overcome these issues. In this study, we assessed the safety and efficacy of epidermal growth factor (EGF)-loaded, peptide-decorated liposomes to improve different aspects of placental function, using tissue from healthy control pregnancies at term, and pregnancies complicated by FGR. Phage screening identified a peptide sequence, CGPSARAPC (GPS), which selectively homed to mouse placentas in vivo, and bound to the outer syncytiotrophoblast layer of human placental explants ex vivo. GPS-decorated liposomes were prepared containing PBS or EGF (50–100 ng/mL), and placental explants were cultured with liposomes for up to 48 h. Undecorated and GPS-decorated liposomes containing PBS did not affect the basal rate of amino acid transport, human chorionic gonadotropin (hCG) release or cell turnover in placental explants from healthy controls. GPS-decorated liposomes containing EGF significantly increased amino acid transporter activity in healthy control explants, but not in placental explants from women with FGR. hCG secretion and cell turnover were unaffected by EGF delivery; however, differential activation of downstream protein kinases was observed when EGF was delivered via GPS-decorated vs. undecorated liposomes. These data indicate that targeted liposomes represent a safe and useful tool for the development of new therapies for placental dysfunction, recapitulating the effects of free EGF.
format	article
author	Lewis J. Renshall Frances Beards Angelos Evangelinos Susan L. Greenwood Paul Brownbill Adam Stevens Colin P. Sibley John D. Aplin Edward D. Johnstone Tambet Teesalu Lynda K. Harris
author_facet	Lewis J. Renshall Frances Beards Angelos Evangelinos Susan L. Greenwood Paul Brownbill Adam Stevens Colin P. Sibley John D. Aplin Edward D. Johnstone Tambet Teesalu Lynda K. Harris
author_sort	Lewis J. Renshall
title	Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction
title_short	Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction
title_full	Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction
title_fullStr	Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction
title_full_unstemmed	Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction
title_sort	targeted delivery of epidermal growth factor to the human placenta to treat fetal growth restriction
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/31d09fe8761e42b3bf935d5bee54fcfc
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Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction

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