A Microfluidic Platform for Cavitation-Enhanced Drug Delivery

Abstract

An endothelial-lined blood vessel model is obtained in a PDMS (Polydimethylsiloxane) microfluidic system, where vascular endothelial cells are grown under physiological shear stress, allowing -like maturation. This experimental model is employed for enhanced drug delivery studies, aimed at characterising the increase in endothelial permeability upon microbubble-enhanced ultrasound-induced (USMB) cavitation. We developed a multi-step protocol to couple the optical and the acoustic set-ups, thanks to a 3D-printed insonation chamber, provided with direct optical access and a support for the US transducer. Cavitation-induced interendothelial gap opening is then analysed using a customised code that quantifies gap area and the relative statistics. We show that exposure to US in presence of microbubbles significantly increases endothelial permeability and that tissue integrity completely recovers within 45 min upon insonation. This protocol, along with the versatility of the microfluidic platform, allows to quantitatively characterise cavitation-induced events for its potential employment in clinics.

An empirical experimental investigation on the effect of an external electric field on the behaviour of laser-induced cavitation bubbles

“…where the liquid pressure P L is determined from equation (7), k l and k c are the dielectric constants of the liquid medium and the nanocluster formed respectively. The size of the generated NPs is determined using 48,49 D = V G (2t d À t) + 2x (11) where V G is the growth velocity, t d and t are the laser pulse duration and nucleation time respectively. Using the above models, the effect of the external electric field on the size of NPs has been investigated.…”

“…5 Over the years, cavitation has been applied to medical technology, especially in fields such as ophthalmology, 6,7 biomedicine, 8,9 and drug delivery. 10 Recently, micro fluidic techniques have been enhanced using cavitation, 11 and have been used in nanoparticle synthesis. 12–15…”

“…5 Over the years, cavitation has been applied to medical technology, especially in fields such as ophthalmology, 6,7 biomedicine, 8,9 and drug delivery. 10 Recently, micro fluidic techniques have been enhanced using cavitation, 11 and have been used in nanoparticle synthesis. [12][13][14][15] Cavitation in liquids induced using a laser has been an effective technique for studying cavitation bubble behaviour in the last couple of decades.…”

A 3D printable perfused hydrogel vascular model to assay ultrasound-induced permeability

“…VE-cadherin organization in response to ultrasound has been examined recently by other groups using terminal immunostaining. 78,79 This paper builds off current work in the field by providing, to the best of the authors' knowledge, the first real-time acquisitions of VE-cadherin junctional dynamics under the application of ultrasound.…”

A Microfluidic System of Gene Transfer by Ultrasound

“…Ultrasound-mediated gene delivery, also known as sonoporation, is a recently developed cell membrane permeation technology that has been applied for DNA and drug delivery in cells [ 13 , 14 , 15 , 16 ]. The technology is based on the cavitation effect of ultrasonic waves.…”