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

Abstract

Congestive heart failure, a prominent cardiovascular disease results primarily from myocardial infarction or ischemia. Milrinone (MRN), a widely used clinical drug for heart failure, improves myocardial contractility and cardiac function through its inotropic and vasodilatory effects. However, lacking target specificity, it exhibits low bioavailability and lower body retention time. Therefore, in this study, angiotensin II (AT1) peptide conjugated human serum albumin nanoparticles (AT1-HSA-MRN-NPs) have been synthesized for targeted delivery of MRN to the myocardium, overexpressing AT1 receptors under heart failure. The NPs were surface functionalized through a covalent conjugation reaction between HSA and AT1. Nanoparticle size was 215.2±4.7 nm and zeta potential -28.8±2.7 mV and cumulative release of MRN was ~72% over 24 hrs. The intracellular uptake of nanoparticles and cell viability was studied in H9c2 cells treated with AT1-MRN-HSA-NPs vs the control non-targeted drug, MRN Lactate under normal, hypoxic and hypertrophic conditions. The uptake of AT1-HSA-MRN-NPs in H9c2 cells was significantly higher as compared to non-targeted nanoparticles, and the viability of H9c2 cells treated with AT1-MRN-HSA-NPs vs MRN Lactate was 73.4±1.4% vs 44.9±1.4%, respectively. Therefore, AT1-HSA-MRN-NPs are safe for in vivo use and exhibit superior targeting and drug delivery characteristics for treatment of heart failure.

In Situ Nanoparticle Self-Assembly for Combination Delivery of Therapeutics to Non-Small Cell Lung Cancer

“…1 H NMR spectroscopy was used to confirm Gem, GA, TA, and HSA complexation in G–G@HTA (Figure G). The characteristic peaks were observed for (1) Gem (7.86, 6.10, 4.23, and 3.94 ppm), (2) GA (3.48, 7.54, 6.6, 5.38, 1.36–1.7, 3.16, 5.14, 6.1, 2.33, and 2.52 ppm), (3) TA (1.0968–2.655, 3.4–3.933, 4.1, 4.3, and 6.6–7.09 ppm), , and (4) HSA (1.13–1.969, 2.204–3.829, 4.01, 4.07, 6.7, and 7.01 ppm) (Figure S1). All these peaks are also composed in G–G@HTA, indicating successful self-assembly formation (Figure G).…”

Low extracellular vesicle concentrations predict survival in patients with heart failure

“…The zeta potential is an electrostatic potential at the electrical bilayer surrounding a nanoparticle in solution ( 4 ). It has been shown to play a role in cell culture systems ( 5 ) and in the context of cardiac uptake and drug delivery ( 6 ). Circulating EVs and their cargo biomolecules have been identified as biomarkers and drivers of benign and malignant diseases including heart failure (HF).…”