While a universal definition does not exist, scientists generally consider materials that are 100 nanometers (nm) or less—each nanometer being one-billionth of a meter—as nanomaterials. At this size range, a material’s surface area to volume ratio increases and electrons can become spatially confined, both of which can result in new physical or chemical properties. Companies may incorporate a nanomaterial into a drug product for a variety of reasons: to serve as an active ingredient or to promote product delivery without the nanomaterial directly providing any therapeutic benefit.
Nanotechnology is a rapidly evolving field that is revolutionizing therapeutic capabilities. Some drug products utilizing nanotechnology are already available, such as chemotherapy drugs Doxil and Abraxane, and many other medical applications of nanomaterials are being developed. For example, researchers at University of Colorado Boulder are investigating the use of light-activated quantum dots to treat antibiotic-resistant infections. To provide another example, nanomedicine company, CytImmune, is using gold nanoparticles to deliver chemotherapy drugs directly to cancer cells. The platform, called Aurimune, successfully completed a phase I clinical trial in 2009. The company is gearing up for a phase II clinical trial with Aurimune and is in preclinical trials with a second-generation therapy, which incorporates Taxol, a small molecule chemotherapy.
The Aurimune platform is designed to target tumor necrosis factor (TNF), a cancer-killing agent, to the site of a tumor without it being toxic to the patient. The therapy capitalizes on the fact that tumor blood vessels are inherently leaky, while healthy blood vessels are not. This difference in blood vessel integrity results in higher accumulation of the nanomedicine in tumor tissue over regular tissue, a concept called the enhanced permeability and retention (EPR) effect. Traveling through healthy blood vessels, the gold nanoparticles are too large to escape, reducing toxic side effects. However, the nanoparticle can leak through leaky vessels associated with its target, tumors. Because the precise size of the nanoparticle determines how effectively the nanoparticles reach their target and distribute in the body, consistency in manufacturing is important.
To prevent the nanoparticle from being attacked by the immune system, the company utilizes a Trojan horse strategy in which the gold nanoparticle is surrounded by a shell of thiol-derivatized polyethylene glycol (PEG-thiol). The PEG-thiol absorbs water, creating a barrier around the nanoparticle and preventing immune detection. Although the PEG improves delivery, its presence adds to the complexity of the nanomaterial-containing platform, and more attachments would boost the structure’s complexity.
Regardless of its intended purpose as an active or inactive ingredient, the incorporation of a nanomaterial into a drug product may alter the properties of the product in a variety of ways, including how the drug is distributed or expelled from the body. There is a diversity of nanomaterial-containing products being developed, and these products often have properties that differ from their large-scale counterparts. Because of their extremely small size, nanomaterials may have enhanced rates of dissolution and higher bioavailability than products that do not contain nanomaterials. Additionally, nanomaterials interact with proteins in an individual’s blood plasma, which can lead to new physicochemical properties in the body.