Inflammation is the body’s way of protecting itself after serious injury or infection and involves a coordinated cascade of signals between cytokines and immune signalling molecules. Inflammation can sometimes get out of hand though and lead to diseases such as atherosclerosis, or artery hardening. Atherosclerosis mainly occurs in large- to mid-sized arteries and is the underlying cause of heart attacks and strokes.

Atherosclerosis is treated today with small-molecule drugs such as statins that lower the levels of certain lipoproteins in the blood. More recently, researchers have developed antibody treatments against the so-called proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme to achieve the same effect. However, cardiovascular disease is still the leading cause of death worldwide, and new therapeutics that reduce inflammation in specific areas of the body, and especially those that do not adversely affect surrounding healthy tissue in these areas, would be better than existing medications.

Controlled-release polymeric nanoparticles

A team led by Omid Farokhzad at the Harvard Medical School in the US and Ira Tabas of Columbia University is now reporting on controlled-release polymeric nanoparticles that can deliver cytokine interleukin 10 (IL-10) to atherosclerotic plaques. IL-10, also known as human cytokine synthesis inhibitory factor, is an anti-inflammatory cytokine that plays a central role in infection by limiting the extent to which the immune system responds to pathogens, so preventing damage to the host.

The researchers used a technique called rapid microfluidic mixing on a chip in which they reacted an aqueous solution and organic solvent to rapidly precipitate out the nanoparticles and entrap the IL-10 protein within them. In this way, large numbers of uniform, small and robust nanoparticles can be made in a matter of minutes, with the biological protein only being exposed to the solvent for a short period of time.

Reducing inflammation

The nanoparticles have peptides on their surfaces and these are naturally attracted to the extracellular matrix components within atherosclerotic plaques. “The IL-10 payload can be released within the plaques over time, so reducing inflammation by remodelling the plaques’ architecture and making the plaques more stable,” lead author of the paper describing the work Nazila Kamaly tells nanotechweb.org.

Farokhzad, Tabas and colleagues have tested their particles on mice that had been fed a high-fat diet and found that the most potent nanoparticle for reducing plaque inflammation in the animals was one called Col-IV IL-10 NP22. The researchers say they now plan to investigate the precise mechanism of action of these nanomedicines further and validate their results in larger animals.

We have more on cell specific targeting and medical delivery systems coming soon in the Nanotechnology Focus on RNAi delivery.