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

Abstract

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.

Dendritic amphiphilic siRNA: Selective albumin binding, in vivo efficacy, and low toxicity

“…Localization of D-siRNA in the tissues mentioned could be explained by the formation of albumin in the liver, and its increased circulation in interstitial tissues/spaces of the skin, muscle, lung, heart, kidneys, and spleen. 11 , 28 , 29 Apart from the liver, these organs have a continuous endothelium that expresses gp60 abundantly, which is the albumin-binding glycoprotein that could also explain the localization observed. 13 Albumin is also an ample component of lung lining fluids (concentration of about 10% of that found in serum) 30 , 31 This opens up the potential to harness the ability to hijack albumin’s biodistribution to target these organs and spaces.…”

Synthesis and characterization of peptide conjugated human serum albumin nanoparticles for targeted cardiac uptake and drug delivery

“…Though the angiotensin is a major axis in HF, used for drug-targeting by ACE inhibitors or angiotensin receptor blockers, we are yet to study the study the effect of AT1-HSA-MRN-NPs on receptor activity. However, the targeted delivery of MRN via AT1 receptor-mediated endocytosis of the nanoparticles is aimed at treating HF in an effective manner, thus suppressing exactly these potential effects [ 40 ]. The AT1 peptide was conjugated to the HSA surface through a two-step covalent chemical reaction.…”

“…Though the release of milrinone has been extensively studied previously with attempts to extend the release over time, only slight improvements have been observed in this area [ 48 , 49 ]. Hence, drug delivery vehicles are needed for effective delivery of MRN to improve the circulation time and rapid clearance from the body along with a targeted approach to further enhance the cardiac uptake and drug activity [ 40 , 50 ].…”

“…The cell viability of H9c2 cells was investigated at 4, 24 and 48 hours, with MRN Lactate exhibiting higher cytotoxicity as compared to AT1-HSA-MRN-NPs and AT1-HSA-NPs. The toxicity of the nanoparticles, both HSA-FITC-NPs as well as AT1-HSA-MRN-NPs without fluorescent tagging, has been studied in our previous studies, both in vitro as well as in vivo [ 12 , 40 ]. It was found that the nanoparticles were non-toxic and safe to use in animals and with further testing, will show immense potential for patients.…”

Nanomedicine strategies for central nervous system (CNS) diseases

“…These avenues are shown in Figure 2 . Currently, polymer-based and liposome-based NPs have been reported as successful nanoscale systems for drug delivery to many parts of the body, including the heart and liver ( Sun et al, 2022 ; Lomis et al, 2021 ). In addition to drug delivery applications, inorganic nanoparticles, typically gold-NPs, are being used in medical imaging to help visualize images more clearly ( Li and Chen, 2015 ).…”