Inhalation of peptide-loaded nanoparticles improves heart failure
Creators
- Michele Miragoli1
- Paola Ceriotti2
- Michele Iafisco3
- Marco Vacchiano4
- Nicolò Salvarani2
- Alessio Alogna5
- Pierluigi Carullo2
- Gloria Belén Ramirez-Rodríguez3
- Tatiana Patrício3
- Lorenzo Degli Esposti3
- Francesca Rossi6
- Francesca Ravanetti7
- Silvana Pinelli8
- Rossella Alinovi8
- Marco Erreni9
- Stefano Rossi8
- Gianluigi Condorelli10
- Heiner Post11
- Anna Tampieri3
- Daniele Catalucci2
- 1. Humanitas Clinical and Research Center, Department of Medicine and Surgery - University of Parma, Institute of Genetics and Biomedical Research - National Research Council
- 2. Humanitas Clinical and Research Center,Institute of Genetics and Biomedical Research - National Research Council
- 3. Institute of Science and Technology for Ceramics, National Research Council
- 4. Humanitas Clinical and Research Center
- 5. Department of Internal Medicine and Cardiology - Charité University Medicine Berlin, Berlin Institute of Health
- 6. Institute of Materials for Electronics and Magnetism, National Research Council
- 7. Department of Veterinary Science, University of Parma
- 8. Department of Medicine and Surgery, University of Parma
- 9. Humanitas Clinical and Research Center, Humanitas University
- 10. Humanitas Clinical and Research Center,Institute of Genetics and Biomedical Research - National Research Council, Humanitas University
- 11. Department of Internal Medicine and Cardiology - Charité University Medicine Berlin,Department of Cardiology, Contilia Heart and Vessel Centre, St. Marien-Hospital Mülheim
Description
Peptides are highly selective and efficacious for the treatment of cardiovascular and other diseases. However, it is currently not possible to administer peptides for cardiac-targeting therapy via a non- invasive procedure, thus representing scientific and technological challenges. Here we demonstrate that inhalation of small (<50 nm in diameter) biocompatible and biodegradable calcium phosphate nanoparticles (CaPs) allows for rapid translocation of CaPs from the pulmonary tree to the blood stream and to the myocardium, where their cargo is quickly released. Treatment of a rodent model of diabetic cardiomyopathy by inhalation of CaPs loaded with a therapeutic mimetic peptide (MP) that we previously demonstrated to improve myocardial contraction resulted in restoration of cardiac function. Translation to a porcine large animal model provided evidence that inhalation of a peptide-loaded CaP-formulation is an effective method for targeted administration to the heart. Altogether, these results demonstrate that inhalation of biocompatible tailored peptide nanocarriers represents a pioneering approach for the pharmacological treatment of heart failure.
Files
aan6205_ArticleContent_v2_20171117.pdf
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