Fetal membrane transport enhancement using ultrasound for drug delivery and noninvasive detection

Purpose: The purpose of this research was to evaluate the effect of ultrasound on mass transport across fetal membrane for direct fetal drug delivery and sensing of the amniotic fluid in a noninvasive manner. Methods: Post-delivery human fetal membranes (chorioamnion) were used for in vitro experiments, in which the effect of ultrasound on transport across fetal membrane of fluorescent model molecule (250 kDa) was evaluated. Ex vivo experiments were carried out on a whole rat amniotic sac. The model molecule or alpha-fetoprotein was injected into the amniotic sac through the placenta. Transport of these molecules across pre- and post-insonation of the amniotic sac was evaluated. The ultrasound enhancement's mechanism was also assessed. Results: The greatest enhancement in mass transport (43-fold) in vitro was achieved for 5 min of insonation (20 kHz, 4.6 W/cm², 5 mm distance). Ex vivo results showed a rapid increase (23-fold) in mass transport of the model molecule and also for alphafetoprotein following 30 s of insonation (20 kHz, 4.6 W/cm², 5 mm distance). Conclusions: Mass transport across fetal membranes was enhanced post-insonation both in vitro and ex vivo in a reversible and transient manner. We suggest that exterior (to the amniotic sac) ultrasound-induced cavitation is the main mechanism of action.