Pericardial Delivery of Biological Agents

Govea, Alayn; Lee, Randall J.

doi:10.1016/j.jacbts.2017.09.007

Cited by 3 publications

(5 citation statements)

References 27 publications

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“…As a delivery route, the pericardial sac offers potential advantages over the intracoronary, intramyocardial or transendocardial routes, in that it may increase therapy concentration locally with limited systemic exposure, it carries no risk of vascular embolization and is not hindered by lack of coronary patency. For these reasons, it has been used as a promising access to administer different therapies, including antiarrhythmic 27 – 29 , angiogenic 30 or cell therapy 7 , 14 , 16 , 31 , 32 . Similarly, different approaches to access the pericardial sac have been described, including percutaneous, transatrial o with the use of dedicated devices or techniques 33 – 36 .…”

Section: Discussionmentioning

confidence: 99%

The epicardial delivery of cardiosphere derived cells or their extracellular vesicles is safe but of limited value in experimental infarction

Crisóstomo

Báez-Díaz

Blanco-Blázquez

et al. 2021

Sci Rep

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The epicardial administration of therapeutics via the pericardial sac offers an attractive route, since it is minimally invasive and carries no risks of coronary embolization. The aim of this study was to assess viability, safety and effectiveness of cardiosphere-derived cells (CDCs), their extracellular vesicles (EVs) or placebo administered via a mini-thoracotomy 72 h after experimental infarction in swine. The epicardial administration was completed successfully in all cases in a surgery time (knife-to-skin) below 30 min. No significant differences between groups were found in cardiac function parameters evaluated using magnetic resonance imaging before therapy and at the end of the study, despite a trend towards improved function in CDC-treated animals. Moreover, infarct size at 10 weeks was smaller in treated animals, albeit not significantly. Arrhythmia inducibility did not differ between groups. Pathological examination showed no differences, nor were there any pericardial adhesions evidenced in any case 10 weeks after surgery. These results show that the epicardial delivery of CDCs or their EVs is safe and technically easy 3 days after experimental myocardial infarction in swine, but it does not appear to have any beneficial effect on cardiac function. Our results do not support clinical translation of these therapies as implemented in this work.

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Section: Discussionmentioning

confidence: 99%

The epicardial delivery of cardiosphere derived cells or their extracellular vesicles is safe but of limited value in experimental infarction

Crisóstomo

Báez-Díaz

Blanco-Blázquez

et al. 2021

Sci Rep

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show abstract

“…As a delivery route, the pericardial sac offers potential advantages over the intracoronary, intramyocardial or transendocardial routes, in that it may increase therapy concentration locally with limited systemic exposure, it carries no risk of vascular embolization and is not hindered by lack of coronary patency. For these reasons, it has been used as a promising access to administer different therapies, including antiarrhythmic [27][28][29], angiogenic [30] or cell therapy [7,14,16,31,32]. Similarly, different approaches to access the pericardial sac have been described, including percutaneous, transatrial o with the use of dedicated devices or techniques [33][34][35][36].…”

Section: Discussionmentioning

confidence: 99%

Epicardial Delivery of Cardiosphere Derived Cells or Their Extracellular Vesicles in a Relevant Infarcted Swine Model: Safe, Easy but of Limited Effectiveness.

Crisóstomo

Báez-Díaz

Blanco-Blázquez

et al. 2021

Preprint

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The epicardial administration of therapeutics via the pericardial sac offers an attractive route, since it is minimally invasive and carries no risks of coronary embolization. The aim of this study was to assess viability, safety and effectiveness of Cardiosphere-Derived Cells (CDCs), their extracellular vesicles (EVs) or placebo administered via a mini-thoracotomy 72h after experimental infarction in swine. The epicardial administration was completed successfully in all cases in a surgery time (knife-to-skin) below 30 minutes. No significant differences between groups were found in cardiac function parameters evaluated using magnetic resonance imaging before therapy and at the end of the study, despite a trend towards improved function in CDC-treated animals. Moreover, infarct size at 10 weeks was smaller in treated animals, albeit not significantly. Arrhythmia inducibility did not differ between groups. Pathological examination showed no differences, nor were there any pericardial adhesions evidenced in any case 10 weeks after surgery. These results show that the epicardial delivery of CDCs or their EVs is safe and technically easy 3 days after experimental myocardial infarction in swine, but it does not appear to have any beneficial effect on cardiac function. Our results do not support clinical translation of these therapies as implemented in this work.

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“…Epicardial delivery of biological agents loaded onto biomaterials for treatment of a variety of cardiovascular diseases and pathologies is a promising area of research and development [1], [2] .…”

Section: Introductionmentioning

confidence: 99%

“…Standard methods of therapeutic delivery -intravenous, intracoronary and oral -are often limited by tissue uptake and system recirculation [1], [3] . Conversely an epicardial strategy, where therapy is delivered directly to the outer surface of the heart, confers many advantages and can overcome these limitations.…”

Section: Introductionmentioning

confidence: 99%

“…Conversely an epicardial strategy, where therapy is delivered directly to the outer surface of the heart, confers many advantages and can overcome these limitations. In one exemplary configuration of this strategy, a biomaterial loaded with therapeutic agents acts as a reservoir on the surface of the heart, providing sustained release to a localized region, thereby preventing adverse systemic affects and increasing myocardial uptake [1] . A wide variety of therapeutics ranging from small molecules such as amiodarone [4] , epinephrine [5] , dobutamine [6] to larger biomolecules such as peptides [7] , growth factors [3] , exosomes [8] , cells [9], [10], [11], [12], [13] , and gene therapies [14] preloaded onto biomaterials and implanted on the epicardial surface have been investigated in animal models of a range cardiovascular conditions.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Multiscale Experimental and Computational Modeling Approaches to Characterize Therapy Delivery to the Heart from an Implantable Epicardial Biomaterial Reservoir

Shirazi

Islam

Weafer

et al. 2019

Adv Healthcare Materials

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Delivery of therapeutic-laden biomaterials to the epicardial surface of the heart presents a promising method of treating a variety of diseased conditions by offering targeted, localized release with limited systemic recirculation and enhanced myocardial tissue uptake. A vast range of biomaterials and therapeutic agents using this approach have been investigated.However, the fundamental factors that govern transport of the drug molecules from the biomaterials to the tissue are not well understood. Here, the transport of a drug analog from a biomaterial reservoir to the epicardial surface is characterized using experimental techniques and microscale modeling. Using the experimentally determined parameters, a multiscale This article is protected by copyright. All rights reserved. model of transport is developed. The model is then used to study the effect of important design parameters such as loading conditions, biomaterial geometry and orientation relative to the cardiac fibers on drug delivery to the myocardium. The simulations highlight the significance of the cardiac fiber anisotropy as a crucial factor in governing drug distribution on the epicardial surface and limiting factor for penetration into the myocardium. The multiscale model can be useful for rapid iteration of different device concepts and determination which designs for epicardial drug delivery may be optimal and most promising for the ultimate therapeutic goal.

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Pericardial Delivery of Biological Agents

Abstract: Corresponding Author

Cited by 3 publications

References 27 publications

The epicardial delivery of cardiosphere derived cells or their extracellular vesicles is safe but of limited value in experimental infarction

The epicardial delivery of cardiosphere derived cells or their extracellular vesicles is safe but of limited value in experimental infarction

Epicardial Delivery of Cardiosphere Derived Cells or Their Extracellular Vesicles in a Relevant Infarcted Swine Model: Safe, Easy but of Limited Effectiveness.

Multiscale Experimental and Computational Modeling Approaches to Characterize Therapy Delivery to the Heart from an Implantable Epicardial Biomaterial Reservoir

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