Micro- and nanoparticles for treating cardiovascular disease

Suarez, Sophia; Almutairi, Adah; Christman, Karen L.

doi:10.1039/c4bm00441h

Cited by 56 publications

(41 citation statements)

References 94 publications

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“…On the other side, Xie et al (2013) developed a carrier based on dextran-co-gelatin NPs to deliver vascular endothelial growth factor for the treatment of peripheral artery disease. Other researchers used micelles, liposomes, as well as gold NPs for drug delivery (Suarez et al, 2015). However, PLGA NPs are most extensively researched owing to their biocompatibility and biodegradability.…”

Section: Introductionmentioning

confidence: 99%

Formulation and In vitro Interaction of Rhodamine-B Loaded PLGA Nanoparticles with Cardiac Myocytes

Jonderian

Maalouf

2016

Front. Pharmacol.

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This study aims to characterize rhodamine B (Rh B) loaded poly(D,L-lactide-co-glycolide; PLGA) nanoparticles (NPs) and their interactions with cardiac myocytes. PLGA NPs were formulated using single emulsion solvent evaporation technique. The influence of varying parameters such as the stabilizer concentration, the sonication time, and the organic to aqueous ratio were investigated. The diameter, the dispersity, the encapsulation efficiency and the zeta potential of the optimized NPs were about 184 nm, 0.19, 40% and -21.7 mV, respectively. In vitro release showed that 29% of the Rh B was released within the first 8 h. Scanning electron microscopy measurements performed on the optimized NPs showed smooth surface and spherical shapes. No significant cytotoxic or apoptotic effects were observed on cardiac myocytes after 24 and 48 h of exposure with concentrations up to 200 μg/mL. The kinetic of the intracellular uptake was confirmed by confocal microscopy and cells took up PLGA NPs within the 1st hours. Interestingly, our data show an increase in the NPs’ uptake with time of exposure. Taken together, we demonstrate for the first time that the designed NPs can be used as potential probes for drug delivery in cardiac myocytes.

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Section: Introductionmentioning

confidence: 99%

Formulation and In vitro Interaction of Rhodamine-B Loaded PLGA Nanoparticles with Cardiac Myocytes

Jonderian

Maalouf

2016

Front. Pharmacol.

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“…One useful property of injectable biomaterials is their ability to protect and sustain release of therapeutic cargo including growth factors, enzymes and small molecule drugs 3–4 . Processes such as angiogenesis, fibrosis and apoptosis are controlled by precisely tuned spacio-temporal presentation of certain molecules.…”

Section: Introductionmentioning

confidence: 99%

Degradable Acetalated Dextran Microparticles for Tunable Release of an Engineered Hepatocyte Growth Factor Fragment

Suarez

Muñoz

Mitchell

et al. 2016

ACS Biomater. Sci. Eng.

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Injectable biomaterials are promising as new therapies to treat myocardial infarction (MI). One useful property of biomaterials is the ability to protect and sustain release of therapeutic payloads. In order to create a platform for optimizing the release rate of cardioprotective molecules we utilized the tunable degradation of acetalated dextran (AcDex). We created microparticles with three distinct degradation profiles and showed that the consequent protein release profiles could be modulated within the infarcted heart. This enabled us to determine how delivery rate impacted the efficacy of a model therapeutic, an engineered hepatocyte growth factor fragment (HGF-f). Our results showed that the cardioprotective efficacy of HGF-f was optimal when delivered over three days post-intramyocardial injection, yielding the largest arterioles, fewest apoptotic cardiomyocytes bordering the infarct and the smallest infarcts compared to empty particle treatment four weeks after injection. This work demonstrates the potential of using AcDex particles as a delivery platform to optimize the time frame for delivering therapeutic proteins to the heart.

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“…While the exact cause in both studies cannot be definitively determined given even needle penetration into the myocardium can cause ventricular arrhythmias, these studies along with the results of the current study, suggest that the link between material properties and arrhythmia vulnerability should be continued to be carefully studied prior to clinical translation. This study only investigated the impact of hydrogels, but micro- and nano-particles are another commonly used form of biomaterial for treating cardiovascular disease [51]. These particles typically spread well through the interstitial space and consequently should, based on the results of the current study, provide minimal disruption to cardiac conduction.…”

Section: Discussionmentioning

confidence: 99%

Intramyocardial injection of hydrogel with high interstitial spread does not impact action potential propagation

et al. 2015

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Injectable biomaterials have been evaluated as potential new therapies for myocardial infarction (MI) and heart failure. These materials have improved left ventricular (LV) geometry and ejection fraction, yet there remain concerns that biomaterial injection may create a substrate for arrhythmia. Since studies of this risk are lacking, we utilized optical mapping to assess the effects of biomaterial injection and interstitial spread on cardiac electrophysiology. Healthy and infarcted rat hearts were injected with a model poly(ethylene glycol) hydrogel with varying degrees of interstitial spread. Activation maps demonstrated delayed propagation of action potentials across the LV epicardium in the hydrogel-injected group when compared to saline and no-injection groups. However, the degree of the electrophysiological changes depended on the spread characteristics of the hydrogel, such that hearts injected with highly spread hydrogels showed no conduction abnormalities. Conversely, the results of this study indicate that injection of a hydrogel exhibiting minimal interstitial spread may create a substrate for arrhythmia shortly after injection by causing LV activation delays and reducing gap junction density at the site of injection. Thus, this work establishes site of delivery and interstitial spread characteristics as important factors in the future design and use of biomaterial therapies for MI treatment.

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Micro- and nanoparticles for treating cardiovascular disease

Cited by 56 publications

References 94 publications

Formulation and In vitro Interaction of Rhodamine-B Loaded PLGA Nanoparticles with Cardiac Myocytes

Formulation and In vitro Interaction of Rhodamine-B Loaded PLGA Nanoparticles with Cardiac Myocytes

Degradable Acetalated Dextran Microparticles for Tunable Release of an Engineered Hepatocyte Growth Factor Fragment

Intramyocardial injection of hydrogel with high interstitial spread does not impact action potential propagation

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