11 May Using Tumor-homing Peptides To Target Drug Delivery to Placenta
MedicalResearch.com Interview with:
Lynda Harris PhD
Lecturer in Pharmaceutics
University of Manchester
Manchester Pharmacy School
Maternal and Fetal Health Research Centre
MedicalResearch.com: What is the background for this study?
Dr. Harris: Pregnancy complications such as pre-eclampsia and fetal growth restriction remain a problem despite advances in antenatal care, and impact heavily on future health: small size at birth is associated with an increased risk of cardiovascular disease and diabetes in later life. Drugs to improve pregnancy outcome are severely lacking, as pregnant women are considered a high risk cohort by drug companies, who fear expensive lawsuits associated with side effects and teratogenicity. The majority of pregnancy complications are caused by a poorly growing or poorly functioning placenta. A number of potential drugs have been identified that enhance placental function in vitro, and improve fetal growth in animal models; however, there is currently no means of restricting their actions to the placenta, and systemic administration of these drugs to pregnant women is not feasible due to the risk of adverse effects in other tissues. To address this issue, we have identified a series of placental “homing peptides” which we have used to create nanocarriers for targeted delivery of drugs to the placenta.
MedicalResearch.com: What are the main findings?
Dr. Harris: Technology for targeted drug delivery was first developed to selectively deliver chemotherapeutics to tumours. As the placenta behaves a bit like a well controlled tumour, we hypothesised that previously identified tumour homing peptides would also selectively bind to the surface of the placenta. We have demonstrated that this is indeed the case, and we have shown that if the tumour homing peptides are attached to the surface of iron oxide nanoworms or liposomes, these nanoparticles selectively accumulate in the placentas of pregnant mice but do not cross to the fetus and are not detected inother maternal organs. By packaging a growth-promoting drug (insulin-like growth factor-II) inside our peptide-decorated liposomes, we showed that targeted delivery increased placental weight in healthy mice and increased fetal weight in a mouse model of fetal growth restriction. Furthermore, using targeted liposomes was much more effective than administering the drug systemically or in non-targeting liposomes.
MedicalResearch.com: What should readers take away from your report?
Dr. Harris: We have provided proof of principle that it is possible to selectively deliver drugs to the placenta. We have also shown that directly enhancing placental function can also indirectly improve fetal growth.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Harris: We are currently undertaking parallel studies using our placental homing peptides to selectively deliver vasodilators to enhance uterine blood flow in pregnant mice. We anticipate our targeted liposomes could be used to deliver different types of drugs to correct various aspects of placental dysfunction.
MedicalResearch.com: Is there anything else you would like to add?
Dr. Harris: As our targeted liposomes provide a safer way of administering existing drugs and testing new compounds in pregnancy, our hope is that in the longer term, our work will pave the way for more investment in obstetric therapeutics and lead to the first clinically approved therapies for placental dysfunction. We are grateful to all our collaborators who have helped us undertake this work and to the BBSRC, UK for funding the project.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Tumor-homing peptides as tools for targeted delivery of payloads to the placenta
BY ANNA KING, CORNELIA NDIFON, SYLVIA LUI, KATE WIDDOWS, VENKATA R. KOTAMRAJU,LILACH AGEMY, TAMBET TEESALU, JOCELYN D. GLAZIER, FRANCESCO CELLESI, NICOLA TIRELLI,JOHN D. APLIN, ERKKI RUOSLAHTI, LYNDA K. HARRIS
SCIENCE ADVANCES 06 MAY 2016 : E1600349
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