Navigation Links
Researchers develop oral delivery system to treat inflammatory bowel diseases
Date:10/10/2010

Researchers at the Georgia Institute of Technology and Emory University have developed a novel approach for delivering small bits of genetic material into the body to improve the treatment of inflammatory bowel diseases. Delivering short strands of RNA into cells has become a popular research area because of its potential therapeutic applications, but how to deliver them into targeted cells in a living organism has been an obstacle.

In the Oct. 10 advance online edition of the journal Nature Materials, researchers describe how they 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 research was sponsored by the National Science Foundation and National Institutes of Health.

"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.

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.

In the paper, the thioketal nanoparticles were formulated from a new polymer -- poly-(1,4-phenyleneacetone dimethylene thioketal) (PPADT) -- and engineered to have a diameter of approximately 600 nanometers for optimal oral delivery.

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 thioketal nanoparticles loaded with siRNA have a cell toxicity profile similar to nanoparticles formulated from the FDA-approved material poly(lactic-co-glycolic acid) (PLGA)," added Murthy.

In the future, thioketal nanoparticles may become a significant player in the treatment of numerous gastrointestinal diseases linked to intestinal inflammation, including gastrointestinal cancers, inflammatory bowel diseases and viral infections, according to Murthy.


'/>"/>

Contact: Abby Vogel Robinson
abby@innovate.gatech.edu
404-385-3364
Georgia Institute of Technology Research News
Source:Eurekalert  

Related biology news :

1. In Parkinsons disease, brain cells abandon mitochondria, researchers report
2. MIT researchers develop a better way to see molecules at work in living brain cells
3. Scripps researchers, UCSD chemists to create center devoted to chemistrys influence on climate
4. New fisheries system will save about $20 million, Iowa State University researchers find
5. The world is full of darkness, reflected in the physiology of the human retina, Penn researchers say
6. FSU researchers examine how bacteria become resistant to antibiotics
7. Knome Awards Human Exome Sequencing and Analysis to Biomedical Researchers
8. Researchers study sleep apnea and lack of oxygen
9. Bonn researchers use light to make the heart stumble
10. Researchers engineer adult stem cells that do not age
11. OU researchers selected by Navy
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Researchers develop oral delivery system to treat inflammatory bowel diseases
(Date:6/20/2016)... 20, 2016 Securus Technologies, a leading ... for public safety, investigation, corrections and monitoring announced ... it has secured the final acceptance by all ... Managed Access Systems (MAS) installed. Furthermore, Securus will ... be installed by October, 2016. MAS distinguishes between ...
(Date:6/9/2016)... June 9, 2016 Paris ... Teleste,s video security solution to ensure the safety of people ... during the major tournament Teleste, an international ... and services, announced today that its video security solution will ... to back up public safety across the country. The system ...
(Date:6/2/2016)... 2016   The Weather Company , an IBM Business ... industry-first capability in which consumers will be able to interact ... questions via voice or text and receive relevant information about ... Marketers have long sought an advertising solution that can ... personal, relevant and valuable; and can scale across millions of ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... Prostate Cancer Foundation (PCF) is pleased to announce 24 new Young ... cancer. Members of the Class of 2016 were selected from a pool of ... More About the Class of 2016 PCF Young Investigators ... ... ...
(Date:6/23/2016)... , June 23, 2016   EpiBiome , a ... $1 million in debt financing from Silicon Valley Bank ... automation and to advance its drug development efforts, as ... facility. "SVB has been an incredible strategic ... services a traditional bank would provide," said Dr. ...
(Date:6/23/2016)... , ... June 23, 2016 , ... STACS DNA Inc., ... Leader at the Arkansas State Crime Laboratory, has joined STACS DNA as a Field ... DNA team,” said Jocelyn Tremblay, President and COO of STACS DNA. “In further expanding ...
(Date:6/23/2016)... , June 23, 2016 Apellis Pharmaceuticals, ... 1 clinical trials of its complement C3 inhibitor, ... and multiple ascending dose studies designed to assess ... of subcutaneous injection in healthy adult volunteers. ... either as a single dose (ranging from 45 ...
Breaking Biology Technology: