Nanopharmaceuticals, as the name suggests, use nanotechnology as a delivery platform for therapeutic agents. Nanomedicine as a whole has many applications, but drug delivery is one of the most promising. The technology allows developers to create injectable nanoparticles that target specific cells in the body and spare healthy tissue from the potential toxicities associated with many therapies. Moreover, particle design can be tuned to improve the pharmacokinetics (PK) of drugs, allowing for varying degrees of delayed release and/or greater concentrations of drug in blood plasma. In short, nanoparticles have the potential to dynamically deliver high doses of drugs directly to the desired site while maintaining a strong safety profile.
How does it work?
I will try to keep this at a high level—primarily because I am not a bio-chemist. Nanoparticles can be thought of as small capsules (usually less than 100 nanometers) that carry an active pharmaceutical ingredient (API) through the bloodstream to its ultimate destination. Once at the site, the capsules begin to degrade and release the payload packaged within. This gradual degradation process is what allows for the delayed release. The variability of this mechanism and the safety of the particles themselves depend on the chemistry used in the design.
There are two primary types of nanoparticles: lipid based and polymer based. Lipid particles surround API with phospholipids that absorb naturally in the body. This absorption, though considered safer, does not allow for a significant delayed release. Polymer based particles, on the other hand, are metabolized instead of absorbed; this allows for a more sustained release and a more stable particle. Polymer particles require more complex chemistry but are less costly than lipid. Other nanoparticles also include binding mechanisms that latch on to specific cells—similar to other targeted biologics.
Where does it work?
In my descriptions above I have simply stated that the nanoparticles circulate the bloodstream and eventually concentrate in the desired location, but how does that actually happen? The answer lies in the composition and nature of the primary nanoparticle target: solid tumors. Tumors are hideous creatures whose primary goal is to survive and grow, thus tumors are constantly replicating cells and developing new blood vessels. The young tumor blood vessels are exactly where nanoparticles, quite literally, fit in.
Tumor blood vessels have more loosely arranged endothelial cells than the walls of mature healthy tissue. Nanoparticles are strategically designed to be too big for healthy tissue, yet small enough to enter the leaky vasculature of tumors. Combined with the poor drainage of tumors, nanoparticles have a handy one-way passage into the tumor. Once inside, the delayed release can create a sustained inhibition of whatever the given API may inhibit. The question then becomes: what API(s) do you want to use to kill the beast?
Below is an image taken from Cerulean Pharma’s website that illustrates how its nanoparticles enter tumors. Cerulean has a polymer based nanoparticle, CRLX101, which contains camptothecin (a potent chemotherapy drug) as its API.
Does it work?
There are a couple nanopharmaceuticals approved of which I am aware: Abraxane and Doxil. Neither of these is a game changer, but they have at least established some credibility for the technology. It is hard to move the needle in cancer so the likelihood of success will always be low. The ability to package so many different APIs into the technology, however, allows for many shots on goal and increases the likelihood of success significantly.
Even if the platform fails to improve efficacy, nanoparticles could possibly emerge as the default delivery method for all chemotherapy drugs. If the technology truly makes drugs safer, then a reduced toxicity profile for existing chemotherapy drugs would undoubtedly be an improvement in quality of life for patients. The unfortunate challenge for developers, though, is that it would be hard to justify a premium price for a drug that does not improve survival. Sadly, this business reality may delay such a sensible use of the technology.
Overall, the scientific rationale is strong but the clinical potential remains an open question. Just as RNA therapies were expected to revolutionize oncology in the 90's, nanoparticles could end up being a very sexy and frustrating flop. Investors that continue to pour billions into nanomedicine development are certainly expecting big things…hopefully they are right.
------------ About the Author: Don Driscoll ------------------------
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