Improvement of in vitro thrombolysis employing magnetically-guided microspheres
Abstract Significant shortcomings in clinical thrombolysis efficiencies and arterial recanalization rates still exist to date necessitating the development of additional thrombolysis-enhancing technologies. For example, to improve tPA-induced systemic clot lysis several supplementary treatment metho...
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Published in | Thrombosis research Vol. 121; no. 6; pp. 799 - 811 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York, NY
Elsevier Ltd
01.01.2008
Elsevier Science |
Subjects | |
Online Access | Get full text |
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Abstract | Abstract Significant shortcomings in clinical thrombolysis efficiencies and arterial recanalization rates still exist to date necessitating the development of additional thrombolysis-enhancing technologies. For example, to improve tPA-induced systemic clot lysis several supplementary treatment methods have been proposed, among them ultrasound-enhanced tissue plasminogen activator (tPA) thrombolysis which has already found some clinical applicability. The rationale of this study was to investigate whether biodegradable, magnetic spheres can be a useful adjuvant to currently existing tPA-induced thrombolysis and further enhance clot lysis results. Based on an envisioned, novel thrombolysis technology – magnetically-guided, tPA-loaded nanocarriers with triggered release of the shielded drug at an intravascular target site – we evaluated the lysis efficiencies of magnetically-guided, non-medicated magnetic spheres in various combinations with tPA and ultrasound. When tPA was used in conjunction with magnetic spheres and a magnetic field, the lysis efficiency under static, no-flow conditions improved by 1.7 and 2.7 fold for red and white clots, respectively. In dynamic lysis studies, the addition of ultrasound and magnetically-guided spheres to lytic tPA dosages resulted in both maximum clot lysis efficiency and shortest reperfusion time corresponding to a 2-fold increase in lysis and 7-fold reduction in recanalization time, respectively. Serial microscopic evaluations on histochemical sections reconfirmed that tPA penetration into and fragmentation of the clot increased with escalating exposure time to tPA and magnetic spheres/field. These results delineate the effectiveness of magnetic spheres as an adjuvant to tPA therapy accelerating in vitro lysis efficiencies beyond values found for tPA with and without ultrasound. We demonstrated that the supplementary use of magnetically-guided, non-medicated magnetic spheres significantly enhances in vitro static and dynamic lysis of red and white blood clots. |
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AbstractList | Abstract Significant shortcomings in clinical thrombolysis efficiencies and arterial recanalization rates still exist to date necessitating the development of additional thrombolysis-enhancing technologies. For example, to improve tPA-induced systemic clot lysis several supplementary treatment methods have been proposed, among them ultrasound-enhanced tissue plasminogen activator (tPA) thrombolysis which has already found some clinical applicability. The rationale of this study was to investigate whether biodegradable, magnetic spheres can be a useful adjuvant to currently existing tPA-induced thrombolysis and further enhance clot lysis results. Based on an envisioned, novel thrombolysis technology – magnetically-guided, tPA-loaded nanocarriers with triggered release of the shielded drug at an intravascular target site – we evaluated the lysis efficiencies of magnetically-guided, non-medicated magnetic spheres in various combinations with tPA and ultrasound. When tPA was used in conjunction with magnetic spheres and a magnetic field, the lysis efficiency under static, no-flow conditions improved by 1.7 and 2.7 fold for red and white clots, respectively. In dynamic lysis studies, the addition of ultrasound and magnetically-guided spheres to lytic tPA dosages resulted in both maximum clot lysis efficiency and shortest reperfusion time corresponding to a 2-fold increase in lysis and 7-fold reduction in recanalization time, respectively. Serial microscopic evaluations on histochemical sections reconfirmed that tPA penetration into and fragmentation of the clot increased with escalating exposure time to tPA and magnetic spheres/field. These results delineate the effectiveness of magnetic spheres as an adjuvant to tPA therapy accelerating in vitro lysis efficiencies beyond values found for tPA with and without ultrasound. We demonstrated that the supplementary use of magnetically-guided, non-medicated magnetic spheres significantly enhances in vitro static and dynamic lysis of red and white blood clots. Significant shortcomings in clinical thrombolysis efficiencies and arterial recanalization rates still exist to date necessitating the development of additional thrombolysis-enhancing technologies. For example, to improve tPA-induced systemic clot lysis several supplementary treatment methods have been proposed, among them ultrasound-enhanced tissue plasminogen activator (tPA) thrombolysis which has already found some clinical applicability. The rationale of this study was to investigate whether biodegradable, magnetic spheres can be a useful adjuvant to currently existing tPA-induced thrombolysis and further enhance clot lysis results. Based on an envisioned, novel thrombolysis technology – magnetically-guided, tPA-loaded nanocarriers with triggered release of the shielded drug at an intravascular target site – we evaluated the lysis efficiencies of magnetically-guided, non-medicated magnetic spheres in various combinations with tPA and ultrasound. When tPA was used in conjunction with magnetic spheres and a magnetic field, the lysis efficiency under static, no-flow conditions improved by 1.7 and 2.7 fold for red and white clots, respectively. In dynamic lysis studies, the addition of ultrasound and magnetically-guided spheres to lytic tPA dosages resulted in both maximum clot lysis efficiency and shortest reperfusion time corresponding to a 2-fold increase in lysis and 7-fold reduction in recanalization time, respectively. Serial microscopic evaluations on histochemical sections reconfirmed that tPA penetration into and fragmentation of the clot increased with escalating exposure time to tPA and magnetic spheres/field. These results delineate the effectiveness of magnetic spheres as an adjuvant to tPA therapy accelerating in vitro lysis efficiencies beyond values found for tPA with and without ultrasound. We demonstrated that the supplementary use of magnetically-guided, non-medicated magnetic spheres significantly enhances in vitro static and dynamic lysis of red and white blood clots. Significant shortcomings in clinical thrombolysis efficiencies and arterial recanalization rates still exist to date necessitating the development of additional thrombolysis-enhancing technologies. For example, to improve tPA-induced systemic clot lysis several supplementary treatment methods have been proposed, among them ultrasound-enhanced tissue plasminogen activator (tPA) thrombolysis which has already found some clinical applicability. The rationale of this study was to investigate whether biodegradable, magnetic spheres can be a useful adjuvant to currently existing tPA-induced thrombolysis and further enhance clot lysis results. Based on an envisioned, novel thrombolysis technology--magnetically-guided, tPA-loaded nanocarriers with triggered release of the shielded drug at an intravascular target site--we evaluated the lysis efficiencies of magnetically-guided, non-medicated magnetic spheres in various combinations with tPA and ultrasound. When tPA was used in conjunction with magnetic spheres and a magnetic field, the lysis efficiency under static, no-flow conditions improved by 1.7 and 2.7 fold for red and white clots, respectively. In dynamic lysis studies, the addition of ultrasound and magnetically-guided spheres to lytic tPA dosages resulted in both maximum clot lysis efficiency and shortest reperfusion time corresponding to a 2-fold increase in lysis and 7-fold reduction in recanalization time, respectively. Serial microscopic evaluations on histochemical sections reconfirmed that tPA penetration into and fragmentation of the clot increased with escalating exposure time to tPA and magnetic spheres/field. These results delineate the effectiveness of magnetic spheres as an adjuvant to tPA therapy accelerating in vitro lysis efficiencies beyond values found for tPA with and without ultrasound. We demonstrated that the supplementary use of magnetically-guided, non-medicated magnetic spheres significantly enhances in vitro static and dynamic lysis of red and white blood clots. |
Author | Torno, Michael D Liu, Xianqiao Kaminski, Michael D Mertz, Carol J O'Brien, William D Rosengart, Axel J Xie, Yumei Meyers, Robert E |
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Keywords | Magnetic spheres Tissue plasminogen activator Thrombolysis Ultrasound Magnetic field Peptidases Microsphere Serine endopeptidases Enzyme Hydrolases Cardiovascular disease t-Plasminogen activator |
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Snippet | Abstract Significant shortcomings in clinical thrombolysis efficiencies and arterial recanalization rates still exist to date necessitating the development of... Significant shortcomings in clinical thrombolysis efficiencies and arterial recanalization rates still exist to date necessitating the development of... |
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SubjectTerms | Biological and medical sciences Blood and lymphatic vessels Calibration Cardiology. Vascular system Diseases of the cardiovascular system Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Hematology, Oncology and Palliative Medicine Humans Immunohistochemistry Lactic Acid - chemistry Magnetic field Magnetic spheres Magnetics Medical sciences Microspheres Models, Biological Particle Size Plasminogen - analysis Plasminogen - chemistry Polyglycolic Acid - chemistry Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) Surface Properties Thrombolysis Thrombosis - blood Time Factors Tissue plasminogen activator Tissue Plasminogen Activator - analysis Ultrasonics Ultrasound |
Title | Improvement of in vitro thrombolysis employing magnetically-guided microspheres |
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