Inhalation of peptide-loaded nanoparticles improves heart failure

Peptides are recognized for being highly selective and efficacious for the treatment of cardiovascular as well as other diseases but their administration via a non invasive procedure is currently not possible, thus... [ view full abstract ]

Peptides are recognized for being highly selective and efficacious for the treatment of cardiovascular as well as other diseases but their administration via a non invasive procedure is currently not possible, thus representing scientific and technological challenges. Here we demonstrate that inhalation of small sized (<50nm) biocompatible and biodegradable calcium phosphate nanoparticles (CaPs) allows for rapid translocation of CaPs from the pulmonary tree to the blood stream and thus to the myocardium where their cargo is quickly released. In particular, treatment of a rodent model of diabetic cardiomyopathy through inhalation of CaPs loaded with a therapeutic mimetic peptide that we previously demonstrated to improve myocardial contraction resulted in restoration of cardiac function. When translated to large animals, tangible evidence that inhalation of a peptide-loaded CaP-formulation is a safe and valid method of cardio-targeted administration was provided. Altogether, these results demonstrate that inhalation of biocompatible tailored peptide nanocarriers represents a pioneering approach for the pharmacological treatment of heart failure.