Heart of the matter — how can inhalable nanoparticles help in drug delivery?

23 June 2017 09:44

An EU-funded project, Cupido, is researching the application of nanotechnologies in the cardiovascular field. Felicity Thomas explains more…

Cardiovascular diseases (CVDs), such as cerebrovascular disease, coronary heart disease and peripheral arterial disease, are the number one cause of death worldwide, according to WHO.¹ Within Europe, CVDs are the causative factor for more than half of all deaths and is more of a disease burden on the region than that caused by AIDS, tuberculosis and malaria combined.²

Moreover, there is the financial burden to consider. In research published by the Centre for Economic and Business Research (Cebr), the financial impact of CVD on six major European countries was predicted to rise to €122.6 billion by the year 2020.³

Novel approaches required

Currently, for patients with established disease there are several therapeutic options available. These include aspirins, beta-blockers, angiotensin-converting enzyme inhibitors and statins.

However, implementation of these therapeutic options is an issue and as they show several weak points concerning efficacy and longer term benefits, novel approaches are fast becoming necessary.

As the available drug delivery methods are oral and intravenous, the drug is able to circulate the blood stream systematically, which leads to several side effects and a reduction in treatment efficacy. During late-stage disease administration of therapies may become more invasive, for example through catheters or implantable pumps. These drug delivery methods may be uncomfortable and inconvenient for the patient as well as being costly to the healthcare system.

On this note, an EU-funded project that was started in February 2017, Cupido, proposed the use of nanotechnologies within the cardiovascular field.⁴ The aim of the project is to develop inhalable nanoparticles that can deliver a therapeutic directly to the heart through the simple act of breathing it in.

Nanoparticles are tiny particles, between 1 and 100 nanometres in size, which may offer a revolutionary route of administration for cardiovascular therapeutics. Additionally, this method would be the first non-invasive and heart-specific therapeutic approach.

A consortium of expertise

Cupido represents a consortium of six academic research groups, five SMEs, two industries and one pharmaceutical company. By drawing on the combined expertise of the various participants of the project, nanoparticles that are biocompatible and biodegradable are under development that can self-assemble and encapsulate drugs (novel or available) in a suitable format for the treatment of CVD.

These nanoparticles will be administered through inhalation and once they have entered the patients’ lungs will translocate to reach the heart in a quick and efficient way. Once the heart has been reached the drug will be released. The inhalation delivery devices are being developed by pharmaceutical company Nemera.⁵

To specifically target the heart, the nanoparticles will be chemically and magnetically guided. This specificity will reduce the chances of adverse side effects and will lower the amounts of therapeutic compound required.

This four-year project is being funded with €6 million under the EU Horizon 2020 Framework Programme.

The breathing heart

Nanoparticle preparation: Bioactive molecules are encapsulated by negatively charged calcium phosphate nanoparticles, which then act as a drug delivery system through the formation of life-compatible nano-pores allowing cellular internalisation.
Nano-embedded microparticle production and inhalation: Nanosized calcium phosphates (CaPs), that are between the range of 1–3 µm in size, can be deposited at the alveolar level. Transforming these particles into a dry powder allows inhalation and hence transmission into the patients’ lungs. Once there the microparticles will dissolve in the lung fluid.
Nanoparticle release and translocation to the heart: Just as oxygenated blood is transferred from the pulmonary circulation to the heart via the pulmonary vein, the inhaled CaPs will transverse the alveolar-capillary barrier to reach the myocardium.
Monitoring and guidance to the heart: Using radiolabelling, the fate of the nanoparticles and their biodistribution will be monitored in vivo, which will allow the selection of the most promising delivery systems. Aptamers will be employed by Cupido to ensure selective drug delivery to the myocardium thereby avoiding adverse side effects.

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