Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

Abstract

Ultrasound-mediated drug delivery is a novel technique for enhancing the penetration of drugs into diseased tissue beds noninvasively. By encapsulating drugs into microsized and nanosized liposomes, the therapeutic can be shielded from degradation within the vasculature until delivery to a target site by ultrasound exposure. Traditional in vitro or ex vivo techniques to quantify this delivery profile include optical approaches, cell culture, and electrophysiology. Here, we demonstrate an approach to characterize the degree of nitric oxide (NO) delivery to porcine carotid tissue by direct measurement of ex vivo vascular tone. An ex vivo perfusion model was adapted to assess ultrasound-mediated delivery of NO. This potent vasodilator was coencapsulated with inert octafluoropropane gas to produce acoustically active bubble liposomes. Porcine carotid arteries were excised post mortem and mounted in a physiologic buffer solution. Vascular tone was assessed in real time by coupling the artery to an isometric force transducer. NO-loaded bubble liposomes were infused into the lumen of the artery, which was exposed to 1 MHz pulsed ultrasound at a peak-to-peak acoustic pressure amplitude of 0.34 MPa. Acoustic cavitation emissions were monitored passively. Changes in vascular tone were measured and compared with control and sham NO bubble liposome exposures. Our results demonstrate that ultrasound-triggered NO release from bubble liposomes induces potent vasorelaxation within porcine carotid arteries (maximal relaxation 31%±8%), which was significantly stronger than vasorelaxation due to NO release from bubble liposomes in the absence of ultrasound (maximal relaxation 7%±3%), and comparable with relaxation due to 12 μM sodium nitroprusside infusions (maximal relaxation 32%±3%). This approach is a valuable mechanistic tool for assessing the extent of drug release and delivery to the vasculature caused by ultrasound.

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo

“…11 In fact, the ability to control and produce a burst release of the encapsulated drug from liposomes would be extremely advantageous and may prove to be an essential step in providing effective levels of drug in the tumor. 12 Several approaches for triggered drug release from liposomes have been investigated, such as enzyme-activated, 13,14 pH-sensitive, 15,16 lightsensitive, 17,18 ultrasound-triggered, [19][20][21] and thermosensitive liposomes. [22][23][24][25][26][27][28][29][30] Thermosensitive liposomes can be prepared from phospholipids that exhibit a sharp gel-to-liquid crystalline transition.…”

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies

“…132 Gaseous delivery usually relies on simple diffusion across the PFCp shell, but if higher release amounts are desired, PA/US techniques can be used. 165 As previously stated, irradiation of PFCps causes phase change from NDs into MBs. The forceful transition can result in stable cavitation.…”

“…17,43 PFCps can also deliver other gases such as the signaling molecule NO, which can mitigate vascular diseases like atherosclerosis. 165 …”

“…178 Either way, cavitation exerts mechanical stresses on nearby cells and increases permeability of junctions or membranes allowing for increased delivery and uptake, an effect known as sonoporation. 132,165 In one study, DNA containing MBs were able to achieve successful in vivo transfection of neural SCs. Prior to being implanted, neural SCs were loaded with MBs so that each cell had about 1–2 MBs adhered to their membrane or within endosomes.…”

Bubble Liposome: A Modern Theranostic Approach of New Drug Delivery

“…[28,29] NO-ELIPs viably instigated blood vessel expansion in ex vivo models utilizing rabbit and porcine carotid corridors. In both reviews, this impact was improved by ultrasound-fortified NO discharge.…”