CapsuTech. Ltd.

Nazareth, Israel

CapsuTech. Ltd.

Nazareth, Israel
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Gourevich D.,CapsuTech Ltd. | Gourevich D.,University of Dundee | Dogadkin O.,InSightec | Dogadkin O.,University of Dundee | And 6 more authors.
Journal of Controlled Release | Year: 2013

Various mechanisms for ultrasound-mediated targeted drug delivery have been investigated in the past several decades. Cyclodextrins are already known for their ability to encapsulate various drugs in their lipophilic cavity; this paper reports evaluation of the potential of a cyclodextrin-based nanocarrier as a drug delivery vehicle, using cell monolayers in vitro in conjunction with ultrasound as the release mechanism. The application of ultrasound to the cell monolayers results in both thermal and mechanical effects; a current challenge is to differentiate between these effects. Inthis study, the cell uptake routes of doxorubicin encapsulated in the cyclodextrin-based carrier were investigated, examining individually the thermal and the mechanical effects of focused ultrasound for drug release. Exploiting mechanical effects, the uptake of encapsulated doxorubicin into cancer cells was increased by a factor of up to 5.5 when ultrasound was applied. Thermal application of FUS increased the cellular uptake of encapsulated doxorubicin by a factor of up to 9.6. Hyperthermia without focused ultrasound resulted in an increase by a factor of up to 5.7. © 2013 Elsevier B.V. All rights reserved.


Gourevich D.,University of Dundee | Gourevich D.,Capsutech Ltd. | Hertzberg Y.,Tel Aviv University | Volovick A.,University of Dundee | And 5 more authors.
Ultrasound in Medicine and Biology | Year: 2013

Ultrasound-mediated targeted drug delivery has been a subject for a dedicated research activity for several decades. Nevertheless, in vitro studies in this field of research are characterized by their inconsistencies. To improve the repeatability of such experiments, a novel approach of multifocal spot generation was investigated. A multifocal pattern of 16 spots was utilized using an iterative Gerchberg-Saxton algorithm. The pattern was applied to insonate a 96-well Petri dish plate using a clinically available planar-phased array transducer with approximately 1000 elements with a central frequency of 0.55 MHz. The pattern was acoustically characterized and applied to a monolayer of human breast cancer cell line in the 96-well plate. With the help of ultrasonic contrast agents, the intracellular drug uptake was increased by an average factor of 3.5 compared with the control group. © 2013 World Federation for Ultrasound in Medicine & Biology.


Gourevich D.,University of Dundee | Gourevich D.,CapsuTech Ltd | Gerold B.,University of Dundee | Gerold B.,InSightec | And 13 more authors.
Advances in Experimental Medicine and Biology | Year: 2012

Introduction: Recently, ultrasonic drug release has been a focus of many research groups for stimuli responsive drug release. It has been demonstrated that a focused ultrasound (FUS) beam rapidly increases the temperature at the focused tissue area. One potential mechanism of drug targeting is to utilize the induced heat to release or increase penetration of chemotherapy to cancer cells. The efficiency of targeted drug delivery may increase by using FUS beam in conjugation with nano-encapsulated drug carriers. The aim of this study is to investigate the effect of heat and ultrasound on the cellular uptake and therapeutic efficacy of an anticancer drug using Magnetic Resonance Imaging guided Focused Ultrasound (MRgFUS). Materials and Methods: Human KB cells (CCL-17 cells) were seeded into 96-well plates and heat treated at 37-55°C for 2-10 min. Cell viability was determined using the colorimetric MTT assay. The cells were also subjected to MRgFUS and the degree of cell viability was determined. These experiments were conducted using an ExAblate 2000 system (InSightec, Haifa, Israel) and a GE 1.5 T MRI system, software release 15. Results: We have observed a significant decrease in human KB cell viability due to heat (>41°C) in the presence of Doxorubicin (DOX), in comparison with DOX at normal culture temperature (37°C). The synergistic effect of heat with DOX may be explained by several mechanisms. One potential mechanism may be increased penetration of DOX to the cells during heating. In addition, we have shown that ultrasound induced cavitation causes cell necrosis. Discussion and Future work: Further investigation is required to optimize the potential of MRgFUS to enhance cellular uptake of therapeutic agents. A novel delivery nano-vehicle developed by CapsuTech will be investigated with MRgFUS for its potential as a stimuli responsive delivery system. Acknowledgments: This work is supported by an EU FP7 Industrial Academia Partnership Pathway IAPP. © 2012 Springer Science+Business Media B.V.


Xu D.,University of Dundee | Wang L.,University of Dundee | Gourevich D.,University of Dundee | Kabha E.,CapsuTech Ltd. | And 5 more authors.
Chemical and Pharmaceutical Bulletin | Year: 2014

A novel γ-cyclodextrin (γ-CD) based carrier for molecular encapsulation of cancer chemotherapeutic agent doxorubicin (DOX) was synthesized and fully characterized by various analytical approaches. The γ-CD derivative, with a β-naphthyl alanine residue attached in its primary face, exhibits potent binding capacity with DOX. The encapsulation efficiency was assessed under various temperatures and pHs and it was demonstrated that the carrier-DOX inclusion complex is highly stable under a wide range of acidic conditions (pH 1.0-7.0); however, the encapsulated drug is slowly released under hyperthermic conditions (up to 50°C). Cell culture studies showed that the complexation of DOX with the carrier protected the drug from being uptaken by the cells and also greatly reduced its toxicity. Thermo-triggered DOX release was validated and the increase in cellular uptake was observed in in-vitro experiments. We concluded that this novel γ-CD derivative is able to effectively encapsulate DOX and the inclusion is responsive to temperature change, hence renders it a potential encapsulating agent for DOX delivery in combination with hyperthermia treatments. © 2014 The Pharmaceutical Society of Japan.


Gourevich D.,University of Dundee | Gourevich D.,CapsuTech. Ltd. | Gerold B.,University of Dundee | Gerold B.,InSightec | And 13 more authors.
Advances in Experimental Medicine and Biology | Year: 2011

Recently, ultrasonic drug release has been a focus of many research groups for stimuli responsive drug release. It has been demonstrated that a focused ultrasound (FUS) beam rapidly increases the temperature at the focused tissue area. One potential mechanism of drug targeting is to utilize the induced heat to release or increase penetration of chemotherapy to cancer cells. The efficiency of targeted drug delivery may increase by using FUS beam in conjugation with nano - encapsulated drug carriers. The aim of this study is to investigate the effect of heat and ultrasound on the cellular uptake and therapeutic efficacy of an anticancer drug using Magnetic Resonance Imaging guided Focused Ultrasound (MRgFUS). Materials and Methods: Human KB cells (CCL-17 cells) were seeded into 96-well plates and heat treated at 37-55°C for 2-10 min. Cell viability was determined using the colorimetric MTT assay. The cells were also subjected to MRgFUS and the degree of cell viability was determined. These experiments were conducted using an ExAblate 2000 system (InSightec, Haifa, Israel) and a GE 1.5 T MRI system, software release 15. Results: We have observed a significant decrease in human KB cell viability due to heat (>41°C) in the presence of Doxorubicin (DOX), in comparison with DOX at normal culture temperature (37°C). The synergistic effect of heat with DOX may be explained by several mechanisms. One potential mechanism may be increased penetration of DOX to the cells during heating. In addition, we have shown that ultrasound induced cavitation causes cell necrosis. Discussion and Future work: Further investigation is required to optimize the potential of MRgFUS to enhance cellular uptake of therapeutic agents. A novel delivery nano-vehicle developed by CapsuTech will be investigated with MRgFUS for its potential as a stimuli responsive delivery system. © 2012 Springer Science+Business Media B.V.


Gourevich D.,University of Dundee | Gourevich D.,Capsutech Ltd. | Volovick A.,University of Dundee | Volovick A.,InSightec | And 7 more authors.
Ultrasound in Medicine and Biology | Year: 2015

Ultrasound-mediated targeted drug delivery is a therapeutic modality under development with the potential to treat cancer. Its ability to produce local hyperthermia and cell poration through cavitation non-invasively makes it a candidate to trigger drug delivery. Hyperthermia offers greater potential for control, particularly with magnetic resonance imaging temperature measurement. However, cavitation may offer reduced treatment times, with real-time measurement of ultrasonic spectra indicating drug dose and treatment success. Here, a clinical magnetic resonance imaging-guided focused ultrasound surgery system was used to study ultrasound-mediated targeted drug delivery in vitro. Drug uptake into breast cancer cells in the vicinity of ultrasound contrast agent was correlated with occurrence and quantity of stable and inertial cavitation, classified according to subharmonic spectra. During stable cavitation, intracellular drug uptake increased by a factor up to 3.2 compared with the control. Reported here are the value of cavitation monitoring with a clinical system and its subsequent employment for dose optimization. © 2015 World Federation for Ultrasound in Medicine & Biology.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-IAPP | Phase: FP7-PEOPLE-IAPP-2008 | Award Amount: 2.07M | Year: 2009

Clinical drug delivery (DD) remains a problem of heightened industrial and academic interest. The proposed partnership seeks to embrace the problem by exploiting the unique expertise-base spanning the industrial research and academic pratners. We will provide inter-sectoral training of mulit-disciplinary researchers and create a novel new DD modality that addresses the key critical needs for non-invasive therapy via intelligent generic targeting and with intrinsic flexibility in drug choice. An essential simplicity to the present approach is that it takes strands of intrinsically safe technologies, and marries these into a powerful amalgam that offers true power and enhanced versatility. Chief amongst the areas of research are: (i) A generic encapsulating technology [CapsuTech - industrial partner] that will vector active anti-cancer drugs to a tumour target; (ii) Remotely triggered drug release on demand by externally focused ultrasound energy [development by industrial partner Insightec](iii) Enhanced drug uptake through the parallel disruption of cell membranes by the action of ultrasound on commercially available microscopic bubbles [sonoporation - University of Dundee]. The Dundee Group, who will lead this partnership, has made significant inroads to fundamental understanding with this latter strand. Moreover, the partners have gone to great lengths to factor in a level of training that also embraces existing trends for image guided intervention: in particular with magnetic resonance imaging (MRI). The project objectives we have realized are fully compatible with MRI technology and indeed, this prescience endows the overall scheme with significant added value. We anticipate that this synergistic and intra-sectoral multi-disciplinary research partnership will create significant momentum, enduring relationships, visionary researchers and a roadmap towards significant European market share, as well as delivering on truly excellent scientific objectives.


PubMed | CapsuTech Ltd
Type: Journal Article | Journal: Journal of controlled release : official journal of the Controlled Release Society | Year: 2013

Various mechanisms for ultrasound-mediated targeted drug delivery have been investigated in the past several decades. Cyclodextrins are already known for their ability to encapsulate various drugs in their lipophilic cavity; this paper reports evaluation of the potential of a cyclodextrin-based nanocarrier as a drug delivery vehicle, using cell monolayers in vitro in conjunction with ultrasound as the release mechanism. The application of ultrasound to the cell monolayers results in both thermal and mechanical effects; a current challenge is to differentiate between these effects. In this study, the cell uptake routes of doxorubicin encapsulated in the cyclodextrin-based carrier were investigated, examining individually the thermal and the mechanical effects of focused ultrasound for drug release. Exploiting mechanical effects, the uptake of encapsulated doxorubicin into cancer cells was increased by a factor of up to 5.5 when ultrasound was applied. Thermal application of FUS increased the cellular uptake of encapsulated doxorubicin by a factor of up to 9.6. Hyperthermia without focused ultrasound resulted in an increase by a factor of up to 5.7.

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