|Targeted nanogels loaded with dexamethasone for pulmonary infection--Courtesy of UPenn Click to enlarge >>|
Researchers at the University of Pennsylvania said they have uncovered a delivery method to treat acute pulmonary inflammation, a condition that afflicts patients suffering from multiple blood transfusions, sepsis, lung surgery and acute lung trauma and has a mortality rate as high as 40%. There is no pharmacological cure for the condition, the scientists said; current treatment involves the use or respirators, which can weaken the lungs over time.
"This [discovery] is a treatment that benefits entirely from targeted delivery or it tends not to have any significant therapeutic benefit," said lead UPenn researcher Dr. David Eckmann in a university news release. "That's part of the challenge with this disorder: We have been uncertain to this point whether it was the medication or its delivery mechanism that wasn't working. Our results in mouse models show beyond a shadow of a doubt that the drugs can be effective, we just needed to improve delivery."
The treatment consists of a hydrophilic nanogel that contains an antibody with an affinity for the lungs, as well as the anti-inflammatory steroid dexamethasone. The antibody used targets the intracellular adhesion molecule, ICAM-1, which is found on the surface of lung endothelial cells, according to study, published in PLOS ONE. "This molecule on the surface of the nanocarrier has specialized preference for the lung to enhance localized and targeted drug delivery," Eckmann said in the news release.
Localized delivery results in improved drug absorption and reduces the side effects of the steroid, the study said. Proving localized delivery and the efficacy of the anti-ICAM-1 antibodies were experiments that found the nanogels loaded with the antibodies targeted the lung 18 times more efficiently than the liver. In addition, nanogels with anti-ICAM-1 antibodies were absorbed by the liver at rate of about 120% of injected dose per gram of tissue, compared to below 15% for control nanogels loaded with the antibody IgG.
The nanogels loaded with the lung targeting antibody and steroid dexamethasone minimized the body's inflammatory response to acute lung injury in mice because the treatment successfully targeted the endothelium, raising hopes that the therapy could someday be applied to treat pulmonary inflammation in humans.