Nanotechnology often is associated with parenteral drug delivery, particularly for anticancer therapies, but it also has applications
in oral drug delivery. Some recent developments show the potential of nanotechnology through this route of administration.
Researchers at the Georgia Institute of Technology (Georgia Tech) and Emory University recently developed a novel approach
for delivering small bits of genetic material into the body to improve the treatment of inflammatory bowel diseases, according
to an Oct. 10, 2010 Georgia Tech press release. Delivering short strands of RNA into cells has potential therapeutic applications,
but delivering them into targeted cells in a living organism has been an obstacle.
In their work, the researchers encapsulated short pieces of RNA into engineered particles called thioketal nanoparticles and
orally delivered the genetic material directly to the inflamed intestines of animals. "The thioketal nanoparticles we designed
are stable in both acids and bases and only break open to release the pieces of RNA in the presence of reactive oxygen species,
which are found in and around inflamed tissue in the gastrointestinal tract of individuals with inflammatory bowel diseases,"
said Niren Murthy, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and
Emory University, in the Georgia Tech press release. This work was done in collaboration with Emory University Division of
Digestive Diseases professor Shanthi Sitaraman, associate professor Didier Merlin, and postdoctoral fellow Guillaume Dalmasso.
The thioketal nanoparticles protect the small interfering RNAs (siRNAs) from the harsh environment of the gastrointestinal
tract and target them directly to the inflamed intestinal tissues. This localized approach is necessary because siRNAs can
cause major side effects if injected systemically. The researchers reported that the thioketal nanoparticles were formulated
from a new polymer—poly-(1,4-phenyleneacetone dimethylene thioketal)—and engineered to have a diameter of approximately 600
nm for optimal oral delivery (1).
For their experiments, the researchers used a mouse model of ulcerative colitis. The researchers orally administered thioketal
nanoparticles loaded with siRNA that inhibits an inflammation-promoting cytokine called tumor necrosis factor–alpha. The nanoparticles
traveled directly to the mouse colons, where reactive oxygen species were being produced in excess, and decreased the cytokine
production levels there. Tissue samples from the colons treated with siRNA delivered by these thioketal nanoparticles exhibited
intact epitheliums, well-defined, fingerlike "crypt" structures, and low levels of inflammation—signs that the colon was protected
against ulcerative colitis.
"Since ulcerative colitis is restricted to the colon, these results confirm that the siRNA-loaded thioketal nanoparticles
remain stable in noninflamed regions of the gastrointestinal tract while targeting siRNA to inflamed intestinal tissues,"
explained Scott Wilson, a graduate student in the Georgia Tech School of Chemical and Biomolecular Engineering, in the press