Targeted nanodelivery of anti-inflammatory drugs
Abstracts
Initial Award Abstract |
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Chronic obstructive pulmonary disease (COPD) is a major killer, accounted for more than 120,000 deaths per year in the United States and for more than 2.7 million deaths per year in the world. Though many factors can contribute to COPD, smoking tobacco is the leading cause of COPD. Smoking leads to inflammation in the lungs, which can lead to COPD and worsen other diseases like asthma. People affected with COPD have greatly restricted lung function, often cough and wheeze, are highly susceptible to lung infections, and have difficulty performing even minor, daily activities due to fatigue and shortness of breath. Tragically, there is no cure for COPD. Quitting smoking is vital to slow the progression of the disease, but current therapies are largely ineffective and can have severe side effects. New therapies are desperately needed. Because inflammation is an important of COPD, new therapies could also benefit other lung inflammatory diseases, such as asthma.
When injected intravenously, most small drugs are diluted over the entire body. They are a very small drop in a large, human-sized bucket. If these therapies could instead be targeted to the lungs and concentrated in the lungs, efficacy could be greatly increased. Unfortunately, most of the ways to target antibodies to a single tissue involve large proteins, which can move easily out of the blood and into the tissue because the inner surface of blood vessels is lined with a tight barrier of cells.
We have shown that there are active shuttles called caveolae that can move drugs across this barrier. We have identified protein markers that are concentrated within caveolae of the lung. These proteins can bind probes that are injected into the blood. Once within caveolae, the probe and any attached cargo is rapidly pumped out of the blood and concentrated in the underlying tissue. Here, we propose that this strategy could be used to target drug carriers to the lungs. Unlike drug alone, the targeted drug would rapidly accumulate only in the lungs. It would then have little to no side effects because the rest of the body never sees the drug. We will first explore anti-inflammatory drugs and determine if incorporation into targeted drug carriers really do make these drugs more effective than free drug against inflammation in the lung.
This novel strategy has great potential for COPD and asthma. The delivery platform is modular, and different components can be assembled in a tinker toy fashion. Thus, different probes can be used to target different organs. Different drugs can be used to treat different diseases. And different drug carriers can be optimized to work best for each disease. This work, therefore, has a broad impact on many single-organ diseases. |
Publications
| Overcoming in vivo barriers to targeted nanodelivery |
| Periodical: Wiley Interdiscip Rev Nanomed Nanobiotechnol |
Index Medicus: |
| Authors: Chrastina A, Massey KA, Schnitzer JE |
ART |
| Yr: 2011 |
Vol: 3 |
Nbr: 4 |
Abs: |
Pg: 421-437 |
| Overcoming in vivo barriers to targeted nanodelivery |
| Periodical: Wiley Interdiscip Rev Nanomed Nanobiotechnol |
Index Medicus: |
| Authors: Chrastina A, Massey KA, Schnitzer JE |
ART |
| Yr: 2011 |
Vol: 3 |
Nbr: 4 |
Abs: |
Pg: 421-437 |
