TY - JOUR
T1 - Inhalation of peptide-loaded nanoparticles improves heart failure
AU - Miragoli, Michele
AU - Ceriotti, Paola
AU - Iafisco, Michele
AU - Vacchiano, Marco
AU - Salvarani, Nicolò
AU - Alogna, Alessio
AU - Carullo, Pierluigi
AU - Ramirez-Rodríguez, Gloria Belén
AU - Patrício, Tatiana
AU - Degli Esposti, Lorenzo
AU - Rossi, Francesca
AU - Ravanetti, Francesca
AU - Pinelli, Silvana
AU - Alinovi, Rossella
AU - Erreni, Marco
AU - Rossi, Stefano
AU - Condorelli, Gianluigi
AU - Post, Heiner
AU - Tampieri, Anna
AU - Catalucci, Daniele
N1 - Publisher Copyright:
Copyright © 2018 The Authors, some rights reserved.
PY - 2018/1/17
Y1 - 2018/1/17
N2 - 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 noninvasive procedure, thus representing scientific and technological challenges. 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 bloodstream 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 that we previously demonstrated to improve myocardial contraction resulted in restoration of cardiac function. Translation to a porcine large animal model provides evidence that inhalation of a peptide-loaded CaP formulation is an effective method of targeted administration to the heart. Together, these results demonstrate that inhalation of biocompatible tailored peptide nanocarriers represents a pioneering approach for the pharmacological treatment of heart failure.
AB - 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 noninvasive procedure, thus representing scientific and technological challenges. 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 bloodstream 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 that we previously demonstrated to improve myocardial contraction resulted in restoration of cardiac function. Translation to a porcine large animal model provides evidence that inhalation of a peptide-loaded CaP formulation is an effective method of targeted administration to the heart. Together, these results demonstrate that inhalation of biocompatible tailored peptide nanocarriers represents a pioneering approach for the pharmacological treatment of heart failure.
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U2 - 10.1126/scitranslmed.aan6205
DO - 10.1126/scitranslmed.aan6205
M3 - Article
C2 - 29343624
AN - SCOPUS:85040862938
SN - 1946-6234
VL - 10
JO - Science translational medicine
JF - Science translational medicine
IS - 424
M1 - Y
ER -