Digestive Diseases News Winter 2011
Drug-loaded Nanoparticles May Offer Precise Targeting in Treatment of Inflammatory Bowel Disease
Research funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) could one day allow doctors to deliver drug-loaded nanoparticles (NPs) in the treatment of inflammatory bowel disease (IBD). Researchers from the Department of Medicine at Emory University engineered NPs to deliver anti-inflammatory agents to the colon and assessed its therapeutic efficacy in a mouse model of colitis.
One of the challenges in treating IBD is targeting the site of inflammation. Another problem is that most existing treatments are associated with significant side effects. “A major advance in therapeutic strategies in diseases such as IBD would be the ability to target drugs to the site of the inflammation in sufficient quantities to maximize local drug concentration and minimize systemic side effects,” stated Hamed Laroui, Ph.D., Division of Digestive Diseases, Department of Medicine, Emory University.
In the past, doctors have had difficulty targeting drugs to the site of inflammation because of the lack of vehicles that could carry sufficient drugs or that could be released at the site of inflammation. In addition, delivering drugs to the colon runs the risk of enzyme degradation and systemic absorption. The researchers decided to use NPs to deliver the anti-inflammatory tripeptide Lys-Pro-Val (KPV).
This study showed KPV-loaded NPs were able to rapidly release KPV, which reduced intestinal inflammation. Because KPV is delivered by NPs in close proximity to the cell membrane, researchers found they could use a low KPV dose. Researchers also showed that KPV-loaded NPs are well protected during transit through the gastric gland and small intestine.
The researchers compared the dose of KPV-loaded NPs with KPV in free solution and found that the effective dose of KPV was 12,000 times lower when administrated via encapsulated KPV-loaded NPs compared with KPV in free solution.
The low dose of KPV raised concern among the researchers whether the concentration was sufficient to reduce intestinal inflammation. They concluded that “KPV-loaded NPs efficiently reduced the severity of intestinal colitis. Given that KPV affects inflammatory responses in both epithelial and immune cells, it is reasonable to suggest that, under the delivery conditions used in the present study, low doses of KPV would affect the inflammatory responses of these two cell types.”
The researchers concluded that encapsulated drug-loaded NPs are a versatile drug-delivery system, with the ability to overcome physiological barriers and target low concentrations of the anti-inflammatory drug KPV to inflamed areas to relieve symptoms of IBD.
The National Digestive Diseases Information Clearinghouse, an information dissemination service of the NIDDK, has fact sheets and easy-to-read booklets about digestive disorders, including IBD. For more information and to obtain copies, visit www.digestive.niddk.nih.gov.
NIH Publication No. 11–4552
Page last updated March 18, 2013