Oral Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

Applying nanopharmacology to reproductive medicine: A novel targeted drug delivery system for the uterus (#76)

Jonathan W Paul 1 2 , Susan Hua 1 2 , Marina Ilicic 1 , Jorge M Tolosa 1 2 , Trent Butler 1 2 , Sarah Robertson 3 , Roger Smith 1 2 4
  1. Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW, Australia
  2. Hunter Medical Research Institute, Newcastle, NSW, Australia
  3. Robinson Research Institute and School of Medicine, University of Adelaide, Adelaide, SA, Australia
  4. Endocrinology Department, John Hunter Hospital, Newcastle, NSW, Australia

Introduction: Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality, while postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide. Both can arise due to dysregulated uterine contractility. Unfortunately, clinical intervention is hampered by the toxicity and lack of specificity of therapeutic agents. Achieving targeted delivery specifically to uterine muscle would improve drug efficacy while minimising side effects.

Liposomes are non-toxic, organic nano-scale vesicles. ‘Targeted liposomes’ are a reliable and versatile platform for targeting drug delivery to specific tissues or organs. We aimed to develop targeted liposomes as a novel targeted drug delivery system for the uterus.

Methods: We coated liposomes with an antibody against the oxytocin receptor (OTR), which is highly expressed on uterine muscle cells during pregnancy. We examined the ability of OTR-targeted liposomes to (i) deliver contraction-blocking or -enhancing agents to human uterine muscle, (ii) localise to pregnant mouse uterine tissue in vivo, and (iii) prevent inflammation-induced PTB in mice.

 Results: OTR-targeted liposomes loaded with contraction-blocking or contraction-enhancing agents abolished or increased human uterine contractions in vitro, respectively. Non-targeted liposomes loaded with these agents had no effect. In vivo, non-targeted liposomes localised only to the liver of pregnant mice. OTR-targeted liposomes exhibited a 7-fold increase in uterine localisation, in addition to the liver localisation. OTR-targeted liposomes were not detected in the maternal brain, heart, kidney or lungs, nor within foetuses. When loaded with indomethacin, OTR-targeted liposomes reduced PTB rates from 67% to 18%. Non-targeted indomethacin-loaded liposomes had no effect.

 Conclusions: OTR-targeted liposomes are a novel drug delivery system for the uterus. Through specifically recognising the OTR, our targeted liposomes facilitate the delivery of contraction-blocking or -enhancing therapeutic agents to uterine muscle. This approach has potential to revolutionise the way therapeutic agents are administered to prevent or promote uterine contractility in pregnant women.