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Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation
- Source :
- Scientific Reports
- Publication Year :
- 2016
-
Abstract
- Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction (AMI), in which the recruitment of inflammatory monocytes plays a causative role. Here we develop bioabsorbable poly-lactic/glycolic acid (PLGA) nanoparticles incorporating irbesartan, an angiotensin II type 1 receptor blocker with a peroxisome proliferator-activated receptor (PPAR)γ agonistic effect (irbesartan-NP). In a mouse model of IR injury, intravenous PLGA nanoparticles distribute to the IR myocardium and monocytes in the blood and in the IR heart. Single intravenous treatment at the time of reperfusion with irbesartan-NP (3.0 mg kg−1 irbesartan), but not with control nanoparticles or irbesartan solution (3.0 mg kg−1), inhibits the recruitment of inflammatory monocytes to the IR heart and reduces the infarct size via PPARγ-dependent anti-inflammatory mechanisms and ameliorates left ventricular remodeling 21 days after IR. Irbesartan-NP is a novel approach to treat myocardial IR injury in patients with AMI.
- Subjects :
- 0301 basic medicine
Myocarditis
Cardiotonic Agents
Myocardial Ischemia
Tetrazoles
Inflammation
030204 cardiovascular system & hematology
Pharmacology
urologic and male genital diseases
Monocytes
Article
03 medical and health sciences
Mice
0302 clinical medicine
Irbesartan
Polylactic Acid-Polyglycolic Acid Copolymer
medicine
Animals
Lactic Acid
Cardioprotection
Drug Carriers
Multidisciplinary
urogenital system
business.industry
Monocyte
Biphenyl Compounds
medicine.disease
female genital diseases and pregnancy complications
Biphenyl compound
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Treatment Outcome
Reperfusion Injury
Immunology
Drug delivery
Nanoparticles
Administration, Intravenous
medicine.symptom
business
Reperfusion injury
Polyglycolic Acid
medicine.drug
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....e68600946c5ec3cccc745392d1986405