A safe way to deliver drugs to the placenta
For the first time, researchers have devised a way to deliver drugs via a pregnant woman's placenta without harming her fetus. This development could help prevent some premature births and treat conditions such as pre-eclampsia.
The University of Manchester scientists have demonstrated that two peptides - chains of amino acids formed when a carboxyl group of one reacts with the amine group of another - originally used to selectively target tumors, will perform the same function in a mouse placenta, delivering drugs which improve placental function and benefit the growing pup fetuses without causing harm.
The paper, "Tumour homing peptides as tools for targeted delivery of payloads to the placenta", is published in the journal Science Advances.
Many pregnancy complications are caused by the placenta not growing or functioning correctly. And currently, no drugs are used to directly target the placenta as a delivery system, such as in pre-eclampsia or fetal growth restriction. Instead doctors induce early delivery of the baby, with increased risk to the neonate of infections and possible cerebral palsy. The Manchester research has the potential to avoid these problems by keeping the fetus inside the mother, avoiding induced labor.
"Placentas behave like well-controlled tumors. They grow quickly, produce growth hormones and evade the immune system.
"A lot of cancer research focuses on finding ways of delivering drugs to kill the tumor without affecting the rest of the body. We had the idea that if we could selectively target the placenta in the same way, we could deliver other drugs which help improve placental function and therefore treat pregnancy complications."
Dr Lynda Harris, Fondazione CEN-European Centre for Nanomedicine, Milan, Italy; Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; and Dipartimento di Chimica, Materiali ed Ingegneria Chimica “G. Natta,” Politecnico di Milano, Milan, Italy, and lead researcher on the paper.
Researchers believe they have demonstrated — in mice — that a growth hormone can be delivered via the placenta, with no visible effect on normal-sized pups, but assisting undersized ones to grow, evidence there is potential for this method to be used in humans.
There were no signs that the drugs delivered built up in the treated pups organs, but instead passed outside of their bodies, as no drugs were found in the mouse fetuses upon delivery. The paper acknowledges that there may be harmful effects to mothers who have undiagnosed cancers, because these drugs will also target their tumors, but the authors suggest a screening program could help overcome this difficulty.
Dr Harris added: "Only one drug for use during pregnancy has been licensed in the last twenty years. By developing this platform we have opened up the possibility of any number of new drugs which can be adapted and then used safely to treat common and serious pregnancy complications."
The availability of therapeutics to treat pregnancy complications is severely lacking mainly because of the risk of causing harm to the fetus. As enhancement of placental growth and function can alleviate maternal symptoms and improve fetal growth in animal models, we have developed a method for targeted delivery of payloads to the placenta. We show that the tumor-homing peptide sequences CGKRK and iRGD bind selectively to the placental surface of humans and mice and do not interfere with normal development. Peptide-coated nanoparticles intravenously injected into pregnant mice accumulated within the mouse placenta, whereas control nanoparticles exhibited reduced binding and/or fetal transfer. We used targeted liposomes to efficiently deliver cargoes of carboxyfluorescein and insulin-like growth factor 2 to the mouse placenta; the latter significantly increased mean placental weight when administered to healthy animals and significantly improved fetal weight distribution in a well-characterized model of fetal growth restriction. These data provide proof of principle for targeted delivery of drugs to the placenta and provide a novel platform for the development of placenta-specific therapeutics.
This is an open access article, freely available online.
The work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC). One of seven Research Councils that work together as Research Councils UK (RCUK). We are funded by the Government's Department for Business, Innovation and Skills (BIS).
Our budget for 2014-2015 is around £509M and we support around 1600 scientists and 2000 research students in universities and institutes across the UK.
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.
Funded by Government, BBSRC invested over £509M in world-class bioscience in 2014-15. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
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May 18, 2016 Fetal Timeline Maternal Timeline News News Archive
Researchers believe they have demonstrated — in mice — a growth hormone delivered via
the placenta, assists undersized mouse pups to grow, with potential for use in humans.
Image Credit:University of Manchester and Science Advances