Sustained release of milrinone delivered via microparticles in a rodent model of myocardial infarction

Kindi, Hamood Al; Paul, Arghya; You, Zhipeng; Nepotchatykh, Oleg; Schwertani, Adel; Prakash, Satya; Shum‐Tim, Dominique

doi:10.1016/j.jtcvs.2014.07.033

Cited by 16 publications

(18 citation statements)

References 33 publications

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“…The AT1-HSA-MRN-NPs were developed for targeted delivery of MRN to the heart [ 10 ]. The overexpression of the AT1 receptors in cardiomyocytes allows for improved targeting of the AT1 peptide and hence greater uptake of the nanoparticle [ 21 ]. The AT1 peptide is an 8-amino acid peptide chain of Asp-Arg-Val-Tyr-Ile-His-Pro-Phe.…”

Section: Resultsmentioning

confidence: 99%

“…The binding of AT1 peptide with HSA was initially characterized by 1 H-NMR ( Figure 2 ). The NMR spectrum of AT1 displays peaks at 6.8–7.0 ppm which are due to the presence of tyrosine residues, while most of the downfield resonance is due to histidine [ 21 ]. Peaks at around 3.5–4.0 ppm due to glycine residues visible on AT1 spectrum are also visible on the AT1-HSA spectrum at around 3.5 ppm.…”

Section: Resultsmentioning

confidence: 99%

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Albumin Nanoparticle Formulation for Heart-Targeted Drug Delivery: In Vivo Assessment of Congestive Heart Failure

et al. 2021

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Congestive heart failure is a fatal cardiovascular disease resulting in tissue necrosis and loss of cardiac contractile function. Inotropic drugs such as milrinone are commonly used to improve the myocardial contractility and heart function. However, milrinone is associated with severe side effects and lower circulation time. In this article, a novel protein nanoparticle formulation for heart-targeted delivery of milrinone has been designed and tested. The formulation was prepared using albumin protein conjugated with the targeting ligand, angiotensin II peptide to form nanoparticles following the ethanol desolvation method. The formulation was characterized for size, charge, and morphology and tested in a rat model of congestive heart failure to study pharmacokinetics, biodistribution, and efficacy. The overall cardiac output parameters were evaluated comparing the formulation with the control non-targeted drug, milrinone lactate. This formulation exhibited improved pharmacokinetics with a mean retention time of 123.7 min, half-life of 101.3 min, and clearance rate of 0.24 L/(kg*h). The targeted formulation also significantly improved ejection fraction and fractional shortening parameters thus improving cardiac function. This study demonstrates a new approach in delivering inotropic drugs such as milrinone for superior treatment of congestive heart failure.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Albumin Nanoparticle Formulation for Heart-Targeted Drug Delivery: In Vivo Assessment of Congestive Heart Failure

et al. 2021

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“…Heat shock protein 27 (HSP27)-loaded PLGA microparticles inside an alginate hydrogel improved cardiac cell protection under hypoxia [234]. PLGA microparticles loaded with milrinone have also been used to improve ejection fraction and reduce inflammation in a rodent MI model [235]. Micro- and nanoparticles based on other biomaterials such as porous silicon, silica, lecithin, pluronic, and dextran have been recently investigated for delivery of proteins to repair the infarcted myocardium [236-239].…”

Section: Controlled Release Systems: Importance and Potential In Cmentioning

confidence: 99%

Towards comprehensive cardiac repair and regeneration after myocardial infarction: Aspects to consider and proteins to deliver

2016

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Ischemic heart disease is a leading cause of death worldwide. After the onset of myocardial infarction, many pathological changes take place and progress the disease towards heart failure. Pathologies such as ischemia, inflammation, cardiomyocyte death, ventricular remodeling and dilation, and interstitial fibrosis, develop and involve the signaling of many proteins. Proteins can play important roles in limiting or countering pathological changes after infarction. However, they typically have short half-lives in vivo in their free form and can benefit from the advantages offered by controlled release systems to overcome their challenges. The controlled delivery of an optimal combination of proteins per their physiologic spatiotemporal cues to the infarcted myocardium holds great potential to repair and regenerate the heart. The effectiveness of therapeutic interventions depends on the elucidation of the molecular mechanisms of the cargo proteins and the spatiotemporal control of their release. It is likely that multiple proteins will provide a more comprehensive and functional recovery of the heart in a controlled release strategy.

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“…A fourth action is that drug encapsulation by MPs can prolong the effects of vasoactive drugs and increase drug concentrations in certain tissues. 8,9 Encapsulation of milrinone within MPs provides a new strategy for drug delivery in patients who have end-stage heart failure. 9 Finally, MPs play an important role in promoting endothelial stability and may serve as biomarkers of endothelial-related disease states.…”

Section: Why Microparticles?mentioning

confidence: 99%

Microparticles and endothelial function—A tour de force

Ferraris

2015

The Journal of Thoracic and Cardiovascular Surgery

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Sustained release of milrinone delivered via microparticles in a rodent model of myocardial infarction

Abstract: Drug encapsulation using microparticles can prolong the effects of milrinone. We propose a new strategy for future drug delivery in patients with end-stage heart failure.

Cited by 16 publications

References 33 publications

Albumin Nanoparticle Formulation for Heart-Targeted Drug Delivery: In Vivo Assessment of Congestive Heart Failure

Albumin Nanoparticle Formulation for Heart-Targeted Drug Delivery: In Vivo Assessment of Congestive Heart Failure

Towards comprehensive cardiac repair and regeneration after myocardial infarction: Aspects to consider and proteins to deliver

Microparticles and endothelial function—A tour de force

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