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Myocardium-targeted liposomal delivery of the antioxidant peptide 8P against doxorubicin-induced myocardial injury.
- Source :
-
International journal of pharmaceutics [Int J Pharm] 2024 Sep 30; Vol. 663, pp. 124569. Date of Electronic Publication: 2024 Aug 08. - Publication Year :
- 2024
-
Abstract
- Doxorubicin (Dox) is a broad-spectrum antineoplastic chemotherapeutic agent used in clinical settings, yet it exhibits significant cardiotoxicity, which in severe cases can lead to heart failure. Research indicates that oxidative stress plays a pivotal role in Dox -induced cardiomyocyte injury. Therefore, the application of antioxidants represents an effective strategy to mitigate the cardiotoxic effects of doxorubicin. In preliminary studies, we isolated an antioxidative peptide, PHWWEYRR (8P). This study utilizes a PCM cardiomyocyte-targeting peptide-modified liposome as a carrier to deliver 8P into cardiomyocytes, aiming to prevent Dox-induced cardiac injury through its antioxidative mechanism. The results demonstrated that we prepared the 8P-loaded and PCM-targeting peptide-modified liposome (P-P-8P), which exhibited good dispersibility, encapsulation efficiency, drug loading capacity, and in vitro release, along with myocardial targeting capability. In vitro experiments showed that P-P-8P could prevent oxidative stress injury in H9C2 cells, protect mitochondrial functions, and inhibit cell apoptosis through a mitochondria-dependent pathway. In vivo experiments indicated that P-P-8P could prevent abnormalities in serum biochemical indicators, cardiac dysfunction, and myocardial pathological changes in mice. In conclusion, P-P-8P effectively delivers 8P to cardiomyocytes, offering protection against the cardiotoxic effects of Dox, and holds potential as a future preventative or therapeutic agent for drug-induced cardiomyopathy.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Male
Mice
Cell Line
Apoptosis drug effects
Cardiotoxicity prevention & control
Cardiotoxicity etiology
Rats
Antibiotics, Antineoplastic administration & dosage
Antibiotics, Antineoplastic toxicity
Myocardium pathology
Myocardium metabolism
Drug Liberation
Drug Delivery Systems
Peptides administration & dosage
Peptides pharmacology
Peptides chemistry
Doxorubicin administration & dosage
Antioxidants pharmacology
Antioxidants administration & dosage
Antioxidants chemistry
Liposomes
Myocytes, Cardiac drug effects
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3476
- Volume :
- 663
- Database :
- MEDLINE
- Journal :
- International journal of pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 39127172
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2024.124569