For their experiments, the researchers used a mouse model of ulcerative colitis -- a debilitating inflammatory bowel disease in which the digestive tract becomes inflamed, causing severe diarrhea and abdominal pain that can lead to life-threatening complications.
The researchers orally administered thioketal nanoparticles loaded with siRNA that inhibits an inflammation-promoting cytokine called tumor necrosis factor - alpha (TNF-α). 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 lower 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 non-inflamed regions of the gastrointestinal tract while targeting siRNA to inflamed intestinal tissues," explained the paper's lead author Scott Wilson, a graduate student in the Georgia Tech School of Chemical & Biomolecular Engineering.
The paper showed that thioketal nanoparticles have the chemical and physical properties needed to overcome the obstacles of gastrointestinal fluids, intestinal mucosa and cellular barriers to provide therapy to inflamed intestinal tissues, he added.
The researchers are currently working on increasing the degradation rate of the nanoparticles and enhancing their reactivity with reactive oxygen species. The team also plans to conduct a biodistribution study to detail how the nanoparticles travel through the body.
"Polymer toxicity is something we'll have to investigate further, but during this study we discovered that thioketa
|Contact: Abby Vogel Robinson|
Georgia Institute of Technology Research News