In this review, researchers present recent advances to the understanding the development of calcium phosphate nanoparticles for targeted, therapeutic delivery in patients suffering from cardiovascular disease, a space where current treatments leave patients.

In particular, the researchers highlight the biocompatibility, bio-degradability and drug-loading versatility of calcium phosphate nanoparticles, and also provide an overview of early-stage animal studies which demonstrate their potential as effective, safe and quick-acting therapies for the treatment of serious cardiovascular conditions, without off-target, systemically-toxic effects

In this study, the team discuss how inhalation, delivering drugs through the lungs, can be used to target the heart for treatment of cardiac disease. This novel approach, called “cardiovascular inhalation,” uses specialized drug formulations and nanocarriers to move medicines from the lungs directly into the heart via the bloodstream. It may offer a safer, less invasive, and more patient-friendly alternative to current methods.

In this article the research team demonstrated that daily inhalation of a novel nano-in-micro peptide therapy, delivered from lung to heart, significantly improved cardiac function in a clinically relevant pig model of chronic heart failure. The targeted delivery system effectively restored heart pumping ability, reversed harmful cardiac remodelling and fibrosis, reduced lung congestion, and repaired disrupted calcium channel trafficking. These results highlight a promising noninvasive treatment strategy for patients with heart failure, giving researchers confidence that similar effects could be achieved in humans and offering potential to modify disease progression and improve outcomes.

In this editorial, Prof. Jean-Sébastien Hulot and Christian Kupatt MD

In this article, Italian researchers reviewed several of the then in-development aptamers, classifying them into various therapeutic indications.

The review argues that aptamers have uses both in cardiovascular diagnostics and treatments and that, compared to other modalities like antibody drug conjugates, they represent potentially much more efficacious and safe candidates for future drug development.

In this study, researchers investigated whether calcium phosphate nanoparticles loaded with biologically-relevant substances can be formulated into a highly breathable dry powder, designed for deep lung deposition, allowing the nanoparticles and their cargo to enter the bloodstream via the pulmonary vein and target cardiac cells.

The researchers developed dry powder formulations composed of mannitol-based microparticles embedding the peptide-loaded calcium phosphate nanoparticles. They demonstrated that these mannitol-based microparticles are highly respirable, and that the in vitro the released nanoparticles are effective for intracellular delivery and  peptide release, supporting potential therapeutic applications.

In this study, researchers from both Italy and the UK investigated whether delivery of the cell-permeable mimetic peptide, R7W-MP could provide protective cardiac benefits in sepsis-induced cardiomyopathy.

In mice treated with lipopolysaccharide, a component of gram negative bacteria and a key driver of sepsis, the development of cardiomyopathy was prevented by administration of R7W MP.  These findings suggest that MP-based therapies targeting the LTCCs could provide new ways to protect the heart during severe and acute infections.

In this study, researchers presented a proof-of-concept approach for the calcium phosphate (CaP) nanoparticle-based delivery of the therapeutic micoRNA, miR-133a, which is downregulated in preclinical models and patients with heart failure.

Mice subjected to transverse aortic constriction, a model of heart failure, were treated with synthetic miR-133a mimic that was encapsulated with CaP-NP and administered via pulmonary nebulisation. The treatment protected the mice against pathological cardiac remodelling and slowed the progression of heart failure without a build up of miR-133a in their livers.

In this study, researchers explored whether the mimetic peptide (MP) they had developed in previous studies could correct the molecular defects caused by two newly identified mutations in the CACNA1C gene,  which encode the calcium channels LTCC and is linked to Brugada syndrome (BrS), BrS an arrhytmogeinc condition that can lead to sudden cardiac death in young adults with structurally normal hearts.

By restoring the proper trafficking, membrane localization, and function of the LTCCs in mutated cells, the MP peptide reversed the loss-of-function BrS phenotype without affecting normal channel properties. This approach opens up the potential for mimetic peptides to become a therapeutic class of their own for patients with inherited mutations impacting cardiac function.

In this paper, the research team demonstrated inhalation of tiny biocompatible calcium phosphate (CaP) nanoparticles represented a faster and more effective delivery method than intravenous injection for reaching the contractile cells (cardiomyocytes)  of the heart. This effect was observed in both rodent and pig models.

In studies conducted in a mouse model of diabetic cardiomyopathy, inhalation of MP-loaded CaP resulted in improved heart performance and was well tolerated, showing no adverse effects. The findings suggest that peptide-loaded nanoparticle inhalation could become a pioneering strategy for treating heart failure and other cardiac diseases.

In this study the research team showed that a specially designed peptide, called Mimetic Peptide (MP), can correct the malfunctioning calcium channels (LTCC) on heart cells. This intervention increases the number of functional channels on the cardiomyocytes surface and restores proper contractile function in a mouse model of diabetic cardiomyopathy. The underlying molecular mechanism was also identified in heart biopsies from heart failure patients, supporting the therapy’s relevance for patients. By targeting LTCCs, the mimetic peptide prevents the loss and internalization of these channels and reverses the impaired heart function caused by disease. This work provides a promising strategy for addressing cardiac disorders that arise from channel defects.

In this study the research team synthesised calcium phosphate (CaP) nanoparticles as a novel, biocompatible and biodegradable delivery system for therapeutics aimed at heart cells. Through an efficient biomineralization inspired method they generated nanoscale carriers capable of safely encapsulating and transporting microRNAs to cardiomyocytes in both laboratory and animal models. The nanoparticles showed excellent biocompatibility, caused no toxicity and did not interfere with cellular function or with the essential electrophysiological properties of cardiac cells.

Following this, the researchers used these same CaP nanoparticles’ to encapsulate microRNAs, which are potential regulators of cardiovascular disease. The researchers were successful in these efforts, demonstrating that they had developed a potential drug delivery method for many of the most complex-to-deliver types of therapeutic agent.