Inhalable therapy for cardiovascular diseases
Cardiovascular diseases pose a significant health problem and a socioeconomic burden to healthcare systems worldwide. First-line oral and intravenous treatments achieve systemic drug circulation that, however, causes several side effects and reduces drug efficacy. Moreover, available treatments address merely the symptoms, underscoring the importance of developing disease-modifying drugs.
Inhalable nanoparticles facilitate drug delivery to the heart
To address the medical need for new drug delivery approaches, the EU-funded CUPIDO project has developed inhalable nanoparticles. “Our innovative nanotechnology based approach can deliver a therapy directly to the diseased heart, overcoming associated side effects of systemic drugs,” explains project coordinator Daniele Catalucci. The research team generated biocompatible, bioinspired, and biodegradable nanoparticles based on calcium phosphate. These have the capacity to self-assemble and encapsulate drugs. The CUPIDO team built on the observation that inhaled combustion derived ultrafine nanoparticles in polluted air were detected in the heart. Project scientists decided to exploit the same mechanism but to deliver a therapeutic instead. The rationale was to use nanoparticles as inhalable nanocarriers to facilitate the delivery of drugs across biological barriers and their release within cardiac cells. Nanoparticles first reach the lungs and then translocate through the bloodstream to the myocardium.
Non-invasive delivery of peptides for improving heart failure
Peptides constitute a promising targeted treatment approach for many diseases, including cardiovascular diseases. However, delivery of peptides to the heart requires an invasive procedure. With the use of nanoparticles, CUPIDO has successfully generated a non-invasive approach for delivering mimetic peptides to the myocardium capable of improving cardiac contractility. The inhalation approach has the potential to provide a faster, more efficient, and patient-friendly delivery of a therapeutic to the heart. It also requires lower drug doses per administration, not only because of more specific targeting to the heart but also because it protects drugs from adverse systemic and gastric degradation. Moreover, fewer side effects caused by unspecific targeting to other organs are expected. Scientists generated various pilot nanoformulations and tested them in both mouse and porcine models of heart failure, with promising results. A one-a-day administration of an innovative bioactive molecule in a pilot-scale breathable therapeutic formulation led to a significant restoration of cardiac function, offering a cure after heart failure. Efficient targeting can be enhanced by aptamers that are specific for the myocardium and promote cell internalisation. Functionalisation of nanoparticles with these aptamers facilitates drug delivery inside the cells.
Nanomedicine for cardiovascular diseases
The application of nanotechnology in the health sector, referred to as nanomedicine, is expected to increase in the near future. Some nanopharmaceuticals have already been approved in health care with promising results. Considering that cardiovascular diseases constitute a leading cause of mortality, with over 26 million deaths worldwide, they surely are the next target for nanomedicine. “CUPIDO had a twofold success, a consolidated team spirit and the production of an innovative therapeutic approach, not yet exploited in any clinical strategy of cardiovascular medicine,” emphasises Catalucci. The next step is to create a start-up fully dedicated to the completion of all the necessary R&D and regulatory requirements.
Keywords
CUPIDO, cardiovascular disease, peptides, nanomedicine, drug delivery, inhalable nanoparticles, aptamers, inhalable therapy
