A revolutionary method of delivering drugs specifically to the uterus, using antibody-coated nanoparticles, has been pioneered by researchers from the University of Newcastle (UON) and Hunter Medical Research Institute.
The technology may allow a new generation of labour drugs to be employed, while existing therapies that deter or induce contractions can potentially be administered in lower dosages with reduced toxicity and fewer off-target effects.
In a world-first study just published in the American Journal of Obstetrics and Gynaecology, pregnancy researchers Dr Jonathan Paul and Laureate Professor Roger Smith AM and nanopharmaceutical specialist Dr Susan Hua successfully targeted a hormone sensor predominantly found in the uterine muscle.
“We’ve known from our research over many years that the uterus expresses the Oxytocin receptor during the labour process. Liposomes [nanoparticles] were the missing piece of the puzzle because you can load them with all kinds of drugs,” Laureate Professor Smith said.
“In this case we covered the liposomes with an antibody to the Oxytocin receptor, which targets the uterus like a guided missile without causing collateral damage.
“We can load it with drugs for relaxation of the uterus to prevent pre-term labour. Or we can encapsulate drugs that bring on labour, or perhaps constrict the uterus in patients who are haemorrhaging after they’ve delivered their baby.”
Higher drug dosages currently given to expectant mothers sometimes impact other organs throughout the body and potentially the unborn baby, Laureate Professor Smith explained.
“In the past, for example, Ventolin was commonly used to relax the uterus muscle and prevent premature labour but it could also cause tremors and even heart failure. It’s no longer used, whereas if encapsulated in liposomes delivered just to the uterine muscle it is not likely to cause the same side effects on the mother.”
Dr Paul and Dr Hua spent four years optimising and evaluating the system in both laboratory modelling and human uterine muscle tissue collected from patients undergoing a caesarean section at the John Hunter Hospital in Newcastle.
“While we haven’t reached the stage of injecting liposomes into pregnant women, it’s a giant leap forward for personalised therapies for mothers,” Dr Paul said. “The liposomes we’re working with are relatively stable and our modelling shows the drugs don’t transfer across the placenta.
“The next thing on our radar are further safety studies before clinical trials, and also characterising the biodistribution. In other words, how quickly do the liposomes get to the uterus and how long do they persist. The other important aspect is demonstrating that we can reduce maternal and foetal side effects.”
Dr Paul won the President’s New Investigator Award at the Society for Reproductive Investigation meeting in the United States last year for his work on the NHMRC-funded project. Dr Hua was the recipient of the 2015 HMRI Early Career Researcher Award.
* Laureate Professor Roger Smith AM, Dr Jonathan Paul are from the UON’s Mothers and Babies Research Centre, researching in conjunction with HMRI’s Pregnancy and Reproduction Program. Dr Susan Hua is from the School of Biomedical Sciences and Pharmacy, Therapeutic Targeting Research Group. HMRI is a partnership between the University of Newcastle, Hunter New England Health and the community.