Heart disease is one of the most common pathological conditions in the human body. Cardiac tissue can be damaged through any number of means, including genetic predispositions, lifestyle choices, and infection. Research into new and novel applications to provide therapeutic and regenerative benefits has been ongoing for many years now. One approach recently has been the use of microparticles.
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Microparticles: an overview
Microparticles are small in size, in the range of 1-1000 μm. They are commonly found in nature, occurring as pollen, dust, sand, flour, as well as in biological cells where they play roles in biologically important functions including being involved in apoptosis, cell activation, cell signaling, and autoimmune responses. Synthetic microparticles have been developed to perform a number of functions.
Microparticles have useful physical and chemical properties that make them suitable for a variety of applications. Their small volume compared to their surface area is especially desirable. They can also be engineered to give them specific properties that are tailored to the task they are needed to perform.
This can include resistance or susceptibility to low or high temperatures, insolubility or solubility in organic solvents dependant on cross-linking in the chemical structure, specific porosity of the surface membrane, high monodispersity and uniformity of shape, and many more properties besides.
Within the biomedical sciences, the ability to engineer microparticles based on synthetic or natural materials is pushing the science to the forefront of the field and is finding new cutting-edge solutions for drug delivery, gene therapy, and a myriad of therapies.
Cardiovascular disease: a major global health problem
Cardiovascular disease is the leading cause of death worldwide. According to the World Health Organization, around 18 million people die each year, an estimated 31% of all deaths globally. Four out of five instances of cardiovascular fatalities are from heart attacks and strokes, and about one-third of them occur in people under 70 years of age.
Those who suffer from raised blood pressure and obesity, and people who make unhealthy lifestyle choices including smoking, are at particular risk, but congenital heart defects can cause early death as well.
Pathologies resulting in atherosclerosis and coronary artery disease lead to myocardial cell death following myocardial infarction. Furthermore, after cell death, the cardiac muscle tissue does not regenerate overall and is replaced by connective tissue, which is non-contractile. This causes weakening of the heart muscle, which is then unable to fully contract and thus heart failure usually follows.
Traditionally, the main approach to treating cardiovascular disease has been the use of pacemakers and heart transplants. However, these approaches are not without their problems: pacemakers have to be replaced and maintained, which can prove costly and may require repeat visits to the hospital; and heart transplants can be difficult to source and can be rejected by the patient. New approaches are therefore clearly needed.
Utilizing microparticles for cardiac muscle repair and therapy: a new approach
For over 50 years, scientists and physicians have been carrying out research into ways to repair cardiac muscle following a heart attack. There have been several medications and procedures developed that have significantly improved heart function, but none have had the ability to actively regenerate damaged cardiac muscle. Current, widely used therapies do not give patients the desired degree of pre-heart attack activity levels. The use of micro- and nanoscale particles has recently been explored.
Cardiac muscle repair
MicroRNA has been explored as one possibility. This is due to the role microRNAs play in the regulation of gene expression as well as their involvement in modifications at the post-transcriptional level. Microparticles can aid in the delivery of microRNA, leading to the proliferation of cardiomyocytes, which are cells that make up cardiac muscle, leading to tissue regeneration. The most potent microRNAs found include human miR-1825 and miR-99a-5p.
Another promising approach has been the use of biodegradable microparticles to deliver neuregulin, a growth factor that aids in inducing cell differentiation and growth into infarcted cardiac tissue. The microparticles used are formed from polylactic glycolic acid and polyethylene glycol, and they slowly degrade over a period of 12 weeks, releasing the neuregulin in a slow and controlled manner.
Another useful element of these microparticles is that they are resistant to immune cells, providing advantages for targeted delivery. Delivering the particles via a spray method as a biodegradable “glue” has been explored.
Other possibilities have been explored in the field of stem cell research and delivering/transplanting them into infarcted cardiac tissue so that new muscle cells can be formed and proliferate. Microparticles clearly can play a role in controlled and targeted delivery to these cells.
Detoxifying cardiac muscle
Further research has been carried out into the detoxification of defective heart muscle. In research published online in 2020, a team led by Zhenhua Li described the use of artificial platelet microparticles to deliver IL-1 β blockers in a targeted way. IL-1 β (Interleukin-1β) is involved in the body’s inflammatory response to an acute myocardial infarction.
Conventional blockers lack the specificity of targeting, which can lead to serious detrimental side-effects. The team hopes that by delivering the blockers in this way they can bind to the injured heart and provide an efficient detoxification method for injured cardiac muscle.
Heparin microparticles used to deliver bone morphogenetic protein - Image Credits: Marian Hettiaratchi / EurekAlert.com
Heart disease is a public health problem that affects millions of people worldwide, leading to reduced quality of life and untimely death for many.
Targeted therapies that aim to repair cardiac muscle and provide efficient levels of detoxification are currently in development, though researchers admit that they have much work to do to understand the mechanisms of heart repair and the potential of these therapies in a practical manner that can aid in the development of the next generation of cardiovascular medicine. Microparticles may provide a unique approach to these issues and provide cutting-edge treatment options.
Topic Overview: Cardiovascular Diseases – World Health Organisation https://www.who.int/health-topics/cardiovascular-diseases/#tab=tab_1
Duelen, R and Sampaolesi, M (2017) Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise EBioMedicine Vol. 16 Pgs. 30-40 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474503/
Kochegarov, A and Lemanski, L.F. (2016) New Trends in Heart Regeneration: A Review J Stem Cells Regen Med Vol. 12 Issue 2 Pgs. 61-68 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5227105/
Li. Z et al. (2020) Targeted anti–IL-1β platelet microparticles for cardiac detoxing and repair Science Advances Vol. 6 No. 6 https://advances.sciencemag.org/content/6/6/eaay0589