Homing peptides: targeting drugs to the placenta

Natalie Cureton, Anna King, Frances Beards, Dr Karen Forbes, Professor Nicola Tirelli, Professor John Aplin, Dr Lynda Harris

Tommy's researchers are using molecular 'postcodes' to target drugs to the placenta that could improve its function during pregnancy.

We already know that certain drugs improve how the placenta works in the lab. However, at the moment there is no way of safely getting these to the placenta in pregnant women. This is because there is no way of delivering the drugs only to the area where they are needed most. For example, when we take a painkiller, the drug circulates throughout the whole body, even though we may only want to treat a headache. This means that drugs are diluted, and can also cause unwanted side effects. 

We are developing a way to target drugs straight to the placenta, so that there is no risk of harm to the unborn child. Every organ in the body has a unique combination of molecules on its surface – a molecular ‘postcode’.

By studying the postcode of the placenta, we have found placenta-specific peptides - these are small molecules that form the building blocks of proteins. When these are injected into the bloodstream of pregnant mice, they only bind to the surface of the placenta and not to any other organ. We call these ‘placental homing peptides’.

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Read more: creating a targeted drug delivery system

To create a targeted drug delivery system, we have made tiny hollow particles called liposomes into which drugs can be packaged. These liposomes are coated with placental homing peptides. When they're injected into the body, they build up in the placenta, releasing their drug cargo only where it is needed. We have tested the liposomes in mice, and have already found that they deliver the drug to the placenta, without it being transferred to the babies. Delivering drugs in this way improved both the blood flow within the womb and the growth of the placenta.

The homing peptides also bind to human placental tissue, so we hope to develop this for the treatment of pregnancy complications in women. We found that some peptides only bind to the blood vessels in the placenta or to the surface of the placenta, which may provide ways to deliver drugs or nutrients to specific parts of the placenta.

In a related project in mice, we have also shown that a drug that relaxes the blood vessels (a vasodilator) can be targeted to the placenta using  liposomes. This improved blood flow in the placenta, and also helped babies to grow better in the womb. When used on samples of human placenta, the drug didn't cause any harm, suggesting it may be a promising new way of improving the health of the placenta in humans. 

Finally, we are carrying out a pilot study looking at how we can use liposomes to deliver molecules that can 'turn off' genes involved in pre-eclampsia or fetal growth restriction. In the longer term, targeted liposomes of this kind could be tested as a treatment for damaged placental function. 

These studies are advancing the development of targeted delivery systems for use in human pregnancy, with the aim of extending the range of drugs that could safely given to treat pregnancy diseases.

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This study takes place in a Tommy's centre and is funded by the Biotechnology and Biological Sciences Research Council

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