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Bleomycin (BLM) is a promising chemotherapeutic that causes oxidative damage to DNA resulting in cell death. However, this non-permeant drug is mainly internalized via receptor-mediated endocytosis. Therefore, tumors showing a poor expression of BLM-binding proteins are resistant to this therapy. This work aims to demonstrate the ability to improve the intracellular accumulation and efficacy of BLM...
The acoustic microstreaming originating from microbubbles' linear oscillations can be used as a potential cell sonoporation tool for drug delivery and gene transfection. However, this bubble-based method suffers from bubble instability, non-uniform size, unreliable performance, and inconvenient trapping. In order to overcome the above drawbacks, in this study, we proposed a massive drug delivery method...
Focused ultrasound enhanced intranasal drug delivery (IN+FUS) is a unique noninvasive approach that utilizes the olfactory pathway to administer drugs directly to the brain. Our group has shown that IN+FUS provides a more homogenous distribution of molecules in the targeted region than intranasal delivery alone. The underlying mechanism of IN+FUS is believed to be due to the microbubble pump effect,...
Video capsule endoscopy (VCE) is a widely accepted clinical alternative to conventional endoscopy for diagnosis in the gut. Its advantages are that it can visualise the entire gastrointestinal tract including the small bowel (SB) and it is less invasive for the patient. However, VCE is suitable only for diagnosis, with little research into therapeutic capsule endoscopy (TCE). Like VCE, TCE has great...
The abnormal vasculature of tumor and the resulting abnormal microenvironment is a major barrier to optimal chemotherapeutic drug delivery. It is well known that ultrasound (US) can increase the permeability of the tumor vessel walls and enhance the accumulation of anticancer drugs. Reconstituted high density lipoproteins (rHDL) nanoparticles (NPs) allow selective delivery of anticancer agents to...
Recently, the diffraction-limit of resolution for ultrasound imaging has been bypassed in-vivo with the localization of microbubbles [Errico et al, Nature 2015]. However, ultrasound therapy remains bound to the half-wavelength limit, imposing a compromise between the therapeutic precision and its penetration. Exploiting threshold phenomena, such as vaporization or cavitation, could provide a solution...
Magnetic Resonance imaging (MRI) guided focused ultrasound (FUS) has been shown to be able to safely ablate deep tissues in the brain in clinical settings resulting in reduction in recovery time and complications. Pre-clinical work has demonstrated that FUS energy deposition with intravascular micro-bubbles could be used also for non-invasive MRI-guided drug delivery into tumours and brain. The preclinical...
Thermal strain imaging (TSI) is promising for lesion targeting and dose control in thermal-based treatment. We previously developed HIFU and temperature sensitive cerasomes (HTSCs) for local chemotherapy of cancer (Liang et al, Acs Nano 2015). However, the temperature within tissues cannot be noninvasively measured in vivo. The aim of this study was to investigate the feasibility of TSI in noninvasive...
Focused ultrasound and microbubbles have been shown to locally and noninvasively open the blood-brain barrier. Despite encouraging results in human patients, several performance and safety features, such as poor drug distribution, high drug accumulation along vessels and small sites of red blood cell extravasation, have been unavoidable. We have recently developed a new ultrasound sequence — rapid...
Acoustically-activated nanodroplets facilitate localized drug delivery after vaporization with improved in vivo stability, drug payload, and minimal interference outside of the ultrasound focal zone compared with microbubbles. They are new acoustic mediators to induce blood-brain barrier (BBB) opening for drug delivery to the brain, with promising potential of extravasation to enhance targeted delivery...
Ultrasound/microbubble (US/MB)-mediated drug delivery is a promising approach to effectively deliver therapeutic agents to target tumors by increasing vascular permeability through sonoporation. Equipped with focused ultrasound, drug delivery platforms can increase site-specificity. To move toward clinical translation, such a platform requires both image guidance for accurate location of tumor targets...
Preclinical studies have shown that MRI-guided focused ultrasound (MRgFUS) can achieve spatially localized thermal exposures in the range of 41–43°C. This presents an advantageous scenario for a plethora of targeted therapeutics. It has been observed that the administration of contrast agent microbubbles (MB) can facilitate increases in temperature with focused ultrasound (FUS), resulting in accelerated...
In previous studies, we have found that addition of cavitation seed such as ultrasound contrast agents (UCA) in sonophoresis accelerate and increase efficiency of transdermal drug delivery (TDD). Actively-induced cavitation with low intensity ultrasound (less than 1 MPa) on the skin causes disordering of the lipid bilayers and the formation of aqueous channels. However, commercial UCAs also have limit,...
The phase transition of nanodroplet has great potential in localized therapy, e.g. gas embolotherapy, drug delivery and the extravascular tumor-targeted theranostics. To improve the temporal and spatial resolution and reduce the energy threshold of nanodroplet phase transition, photoacoustic cavitation (PAC) using synergistic laser and ultrasound was introduced and compared with acoustic droplet vaporization...
Ultrasound-mediated drug delivery using microbubbles is a growing field with applications ranging from targeted chemotherapy delivery to permeating the blood brain barrier. However, the precise parameters that induce increased cellular permeability are not fully understood. For sonoporation efficiency, a high microbubble concentration is preferred, but acoustic shadowing limits the ultrasound delivery...
Studies have shown that treatment of pancreatic ductal adenocarcinoma (PDAC) with systemic administration of gemcitabine (GEM) is inhibited by excessive desmoplastic connective tissue surrounding the tumor. Ultrasound (US) insonification combined with drug-loaded poly lactic acid (PLA) microbubbles (MB) may circumvent this through targeted delivery to the tumor via increased permeability and lodging...
Sonophoresis which utilizes ultrasound for transdermal drug delivery (TDD), can increase the skin permeability and improve the efficiency of drug delivery to various drugs. In addition, the addition of microbubbles in sonophoresis accelerate and increase an efficiency of drug delivery. The cavitation induced by sonophoresis with microbubbles on the skin surface may cause disordering of the lipid bilayers...
Ultrasound-mediated drug delivery using microbubbles is a growing field with applications ranging from targeted chemotherapy to permeating the blood brain barrier. Despite the potential clinical impact of this technique, the precise parameters needed to reliably induce cell sonoporation, or increased cellular permeability, are not well understood. The goal of this work is to use high frame rate imaging...
Despite the progress of focused ultrasound (FUS)-mediated blood-brain barrier (BBB) disruption, neuro-inflammatory responses and the high variability of the FUS transmission through the human skull make the control of the acoustic parameters challenging. In this study, we developed a high-field (7-T) magnetic resonance (MR)-guided FUS system with a feedback control based on passive cavitation detection...
Video capsule endoscopy is a widely accepted clinical alternative to conventional endoscopy for examination of the gastrointestinal tract. Its advantages are that it can visualize the entire gastrointestinal tract including the anatomically remote small intestine and it is less invasive for the patient as compared to conventional endoscopy. However, video capsule endoscopy is suitable only for diagnosis,...
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