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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...
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,...
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 (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...
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,...
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...
Focused ultrasound with nanodroplets could facilitate localized drug delivery after vaporization with potentially improved in vivo stability, drug payload, and minimal interference outside of the focal zone compared with microbubbles. While the feasibility of blood-brain barrier (BBB) opening using nanodroplets has been previously reported, characterization of the associated delivery has not been...
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...
Angelman syndrome (AS) is a rare neuro-genetic disorder caused by loss of expression of the maternal copy of UBE3A in the brain inducing severe mental and physical impairments. Due to brain-specific genetic imprinting, the paternal UBE3A is silenced by a long antisense transcript. Inhibition of the antisense transcript could lead to unsilencing of paternal UBE3A, thus providing a therapeutic approach...
In situ forming implants (ISFIs) can provide continuous, high dose release of chemotherapeutic drug directly at the tumor site. However, poor drug distribution through the tumor volume has limited the effectiveness and subsequent translation of ISFIs into clinical practice. In this study, mice were subcutaneously injected with phase-inverting ISFIs loaded with fluorescein and exposed to therapeutic...
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...
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...
In cancer treatment, there is a need to improve chemotherapeutic drug uptake at the local tumor site to both enhance dose efficacy and minimize any toxic side effects. It is well known now that stably cavitating microbubbles (MBs) in an ultrasound (US) field can increase the permeability of tumor blood vessel walls. This consequently can enhance the extravasation and accumulation of a circulating...
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...
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