scholarly journals Preclinical study to improve microbubble-mediated drug delivery in cancer using an ultrasonic probe with an interchangeable acoustic lens

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seunghyun Lee ◽  
Hoyoon Jeon ◽  
Shinyong Shim ◽  
Maesoon Im ◽  
Jinsik Kim ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Focused Ultrasound ◽  
Pressure Field ◽  
Ultrasound Irradiation ◽  
Radius Of Curvature ◽  
Control Group ◽  
Ultrasonic Probe ◽  
Acoustic Lens ◽  
Concave Lens

AbstractFocused ultrasound with microbubbles (FUS-MBs) has shown that it can lead to an efficient drug delivery system (DDS) involving the oscillation and destruction of the MB but is limited in drug delivery due to its narrow pressure field. However, unfocused ultrasound with MBs (UUS-MBs) and an interchangeable acoustic lens can tune and enhance the pressure field for MB destruction to overcome the disadvantages of FUS-MB DDSs. We designed a lens suitable for an ultrasound-phased array probe and studied the optimal treatment conditions for MB destruction in vitro through an optical imaging setup. The DDS effects were evaluated in a rat hepatoma model using doxorubicin (DOX) treatment. A concave lens with a radius of curvature of 2.6 mm and a thickness of 4 mm was selected and fabricated. UUS-MBs with the acoustic lens at 60 Vpp for 32 cycles and a PRF of 1 kHz could induce MB destruction, promoting the DDS even under fluidic conditions. In the animal experiment, the UUS-MBs in the acoustic lens treatment group had a higher concentration of DOX in the tumor than the control group. Our system suggests uses an acoustic lens to increase DDS effectiveness by providing sufficient ultrasound irradiation to the MBs.

Miniaturized Focused Ultrasound Transducers for Intravascular Therapies

2017 ◽  
Author(s):  
Jinwook Kim ◽  
Huaiyu Wu ◽  
Xiaoning Jiang
Keyword(s):  
Focused Ultrasound ◽  
Radius Of Curvature ◽  
Ultrasound Transducers ◽  
Element Analysis ◽  
Aperture Diameter ◽  
Beam Focusing ◽  
Concave Lens ◽  
Ultrasound Energy ◽  
Forward Looking

Intravascular ultrasound approach has shown its advantages for thrombectomy. Catheter-directed ultrasound techniques have realized safe therapies by suppressing mechanical contact and penetration of excessive ultrasound energy through the tissue. One limitation of this approach is the lack of the sufficient ultrasound energy for fast thrombectomy because typical catheter-mounted transducers have high-frequency and low acoustic power. In this work, we aim to resolve this problem by designing miniaturized focused ultrasound transducers for improved therapeutic efficacy, which can generate low-frequency, sufficient pressure output within the confined insonation beam. This study builds upon our previous initial design of sub-megahertz, forward-looking, focused ultrasound transducers for preliminary in vitro study on microbubble-mediated thrombolysis. 650 kHz, forward-looking, concave-aperture ultrasound transducers were designed and mounted on 5–6 F catheters. The effect of design factors including aperture diameter, radius-of-curvature, and concave lens acoustic impedance on focusing performance were analyzed by using finite element analysis. Although the theoretical prerequisites for ideal beam focusing were not fulfilled due to the spatial limitation, the simulation results showed that practical design of the concave lens with the small geometrical aperture still enables to generate confined beam with a reasonable focal gain. Experimental validation results confirmed that the focal gain of 9 dB can be achievable. The measured transmitting sensitivity of the concave aperture transducer is 22.5 kPa/Vpp.

scholarly journals Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Leela Goel ◽  
Huaiyu Wu ◽  
Bohua Zhang ◽  
Jinwook Kim ◽  
Paul A. Dayton ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Negative Pressure ◽  
Boiling Point ◽  
Clot Lysis ◽  
Control Group ◽  
Peak Negative Pressure ◽  
Blood Clots ◽  
Tissue Plasminogen ◽  
First Time

AbstractOne major challenge in current microbubble (MB) and tissue plasminogen activator (tPA)-mediated sonothrombolysis techniques is effectively treating retracted blood clots, owing to the high density and low porosity of retracted clots. Nanodroplets (NDs) have the potential to enhance retracted clot lysis owing to their small size and ability to penetrate into retracted clots to enhance drug delivery. For the first time, we demonstrate that a sub-megahertz, forward-viewing intravascular (FVI) transducer can be used for ND-mediated sonothrombolysis, in vitro. In this study, we determined the minimum peak negative pressure to induce cavitation with low-boiling point phase change nanodroplets and clot lysis. We then compared nanodroplet mediated sonothrombolysis to MB and tPA mediate techniques. The clot lysis as a percent mass decrease in retracted clots was 9 ± 8%, 9 ± 5%, 16 ± 5%, 14 ± 9%, 17 ± 9%, 30 ± 8%, and 40 ± 9% for the control group, tPA alone, tPA + US, MB + US, MB + tPA + US, ND + US, and ND + tPA + US groups, respectively. In retracted blood clots, combined ND- and tPA-mediated sonothrombolysis was able to significantly enhance retracted clot lysis compared with traditional MB and tPA-mediated sonothrombolysis techniques. Combined nanodroplet with tPA-mediated sonothrombolysis may provide a feasible strategy for safely treating retracted clots.

scholarly journals Tumor Targeted Multifunctional Magnetic Nanobubbles for MR/US Dual Imaging and Focused Ultrasound Triggered Drug Delivery

2020 ◽  
Vol 8 ◽  
Author(s):  
Zhen Jin ◽  
Jinlong Chang ◽  
Peipei Dou ◽  
Shang Jin ◽  
Min Jiao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mr Imaging ◽  
Tumor Targeting ◽  
Focused Ultrasound ◽  
Imaging Modality ◽  
Double Emulsion ◽  
Superparamagnetic Iron Oxide ◽  
Average Diameter ◽  
Control Technique

The development of multifunctional nanoplatforms that are safe and have multiple therapeutic functions integrated with dual- or multi-imaging modality is one of the most urgent medical requirements for active cancer therapy. In our study, we prepared multifunctional magnetic nanobubbles (MF-MNBs) by co-encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) and doxorubicin into polylactideco–glycolide–polyethylene glycol–folate (PLGA-PEG-FA) polymer-based nanobubbles for tumor-targeted ultrasound (US)/magnetic resonance (MR) imaging and focused ultrasound (FUS)-triggered drug delivery. Hydrophobic SPIONs were successfully embedded into MF-MNBs by a typical double emulsion process. The MF-MNBs were highly dispersed with well-defined spherical morphology and an average diameter of 208.4 ± 12.58 nm. The potential of MF-MNB as a dual-modal contrast agent for US and MR imaging was investigated via in vitro study, and the MF-MNB exhibits promising US/MR contrast ability. Moreover, tumor targeting ability was further enhanced by folate conjugation and assessed through in vitro cell test. Furthermore, FUS, as a non-invasive and remote-control technique, was adopted to trigger the release of doxorubicin from MF-MNB and generate the sonoporation effect to enhance drug release and cellular uptake of MF-MNBs. The 4T1 cell viability was significantly decreased by FA ligand-receptor-mediated targeting and FUS sonication. In addition, the developed MF-MNB also exhibits enhanced accumulation in tumor site by FA ligand-receptor-mediated tumor targeting, in which the accumulation of MF-MNB was further enhanced by FUS sonication. Hence, we believe that the MF-MNB could be a promising drug nanocarrier for US/MR-guided anticancer drug delivery to improve cancer treatment efficacy.

scholarly journals Combining Microbubble Contrast Agent with Pulsed-Laser Irradiation for Transdermal Drug Delivery

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 175 ◽  
Author(s):  
Ai-Ho Liao ◽  
Ho-Chiao Chuang ◽  
Bo-Ya Chang ◽  
Wen-Chuan Kuo ◽  
Chih-Hung Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Contrast Agent ◽  
Transdermal Drug Delivery ◽  
Ultrasound Contrast Agent ◽  
Pulsed Laser ◽  
Small Animal ◽  
Skin Permeability ◽  
Control Group

The optodynamic process of laser-induced microbubble (MB) cavitation in liquids is utilized in various medical applications. However, how incident laser radiation interacts with MBs as an ultrasound contrast agent is rarely estimated when the liquid already contains stable MBs. The present study investigated the efficacy of the laser-mediated cavitation of albumin-shelled MBs in enhancing transdermal drug delivery. Different types and conditions of laser-mediated inertial cavitation of MBs were first evaluated. A CO2 fractional pulsed laser was selected for combining with MBs in the in vitro and in vivo experiments. The in vitro skin penetration by β-arbutin after 2 h was 2 times greater in the group combining a laser with MBs than in the control group. In small-animal experiments, the whitening effect on the skin of C57BL/6J mice in the group combining a laser with MBs on the skin plus penetrating β-arbutin increased (significantly) by 48.0% at day 11 and 50.0% at day 14, and then tended to stabilize for the remainder of the 20-day experimental period. The present results indicate that combining a CO2 laser with albumin-shelled MBs can increase skin permeability so as to enhance the delivery of β-arbutin to inhibit melanogenesis in mice without damaging the skin.

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