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

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Drug Delivery Systems*; Milrinone/*pharmacology ; Myocytes, Cardiac/*drug effects ; Nanoparticles/*administration & dosage ; Peptide Fragments/*pharmacology ; Serum Albumin, Human/*chemistry; Animals ; Biological Transport ; Cardiotonic Agents/chemistry ; Cardiotonic Agents/pharmacology ; Cell Survival ; Drug Carriers ; Humans ; Milrinone/chemistry ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; Nanoparticles/chemistry ; Peptide Fragments/chemistry ; Rats

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.
Competing Interests: The authors declare no competing interests.

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0 (Cardiotonic Agents)
0 (Drug Carriers)
0 (Peptide Fragments)
JU9YAX04C7 (Milrinone)
ZIF514RVZR (Serum Albumin, Human)

Date Created: 20210930 Date Completed: 20211119 Latest Revision: 20211119

20240829

PMC8483410

10.1371/journal.pone.0254305

34591850