Prof. Paolo Colombo, CEO of PlumeStars srl, has been invited as speaker at National and Kapodistrian University of Athens on 18th January to present the speech “Nanoparticles lung inhalation as a drug delivery route for heart diseases” to the participants of the annual meeting of the MSc Industrial Pharmacy, a post graduate course directed by Prof. Dimitrios Rekkas. The meeting was very well attended by several representatives of the Greek pharmaceutical companies.
Nanoparticle lung inhalation as a drug delivery route for heart diseases
The lack of disease-modifying drugs going beyond current neuro-hormonal counter regulation is one of the major unmet needs in patients with heart failure (HF). Peptides are highly selective molecules with the potential of a direct impact at cardiomyocyte level. However, a targeted and enhanced delivery to the heart, together with an enriched distribution towards their intracellular cardiomyocytes, is absent.
The intra-tracheal administration of biocompatible and biodegradable peptide-loaded calcium phosphate nanoparticles (CaPs) demonstrated rapid translocation of CaPs to the bloodstream for myocardial release. Here, the first translational insights into the mode of action of CaPs loaded with a mimetic peptide (CaP-MP), in restoring the function of failing heart by modulating impaired L-type calcium channel (LTCC) trafficking, a downstream hallmark of HF, is presented.
Daily inhalation of a mannitol-based microparticles embedding CaP-MP loaded nanoparticles improved cardiac contractility in vitro and in vivo in a clinically highly relevant porcine model of HF. This effect is accompanied by a beneficial structural heart remodeling, as confirmed at a trabecular, cellular, and proteomic level. The overall advantageous effects, safety and tolerability of the inhalable LTCC-modulation point towards a game-changing treatment for HF patients.
Mechanistically, the patient inhales microparticles embedding mimetic peptide loaded calcium phosphate nanoparticles, aerosolized with a portable dry powder inhaler. The microparticles deposited into lung dissolve releasing the nanoparticles, that are insoluble at pH 7.4. Then, nanoparticles translocate through deep lung wall to pulmonary blood to be directly transported to hearth. Here, they can be up taken by the cardiomyocytes where the low pH dissolves the calcium phosphate nanoparticles providing the release of the mimetic peptide.