Journal
GASTROENTEROLOGY
Volume 138, Issue 3, Pages 843-U77Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2009.11.003
Keywords
Colon Targeting; Colitis; KPV-Loaded Nanoparticle; Polysaccharide Hydrogel
Categories
Funding
- National Institutes of Health of Digestive Diseases [R24-DK-064399, R56DK061941, RO1-DK076825, RO1-DK064711]
- Crohn's and Colitis Foundation of America
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BACKGROUND & AIMS: One of the challenges to treating inflammatory bowel disease (IBD) is to target the site of inflammation. We engineered nanoparticles (NPs) to deliver an anti-inflammatory tripeptide Lys-Pro-Val (KPV) to the colon and assessed its therapeutic efficacy in a mouse model of colitis. METHODS: NPs were synthesized by double-emulsion/solvent evaporation. KPV was loaded into the NPs during the first emulsion of the synthesis process. To target KPV to the colon, loaded NPs (NP-KPV) were encapsulated into a polysaccharide gel containing 2 polymers: alginate and chitosan. The effect of KPV-loaded NPs on inflammatory parameters was determined in vitro as well as in the dextran sodium sulfate-induced colitis mouse model. RESULTS: NPs (400 nm) did not affect cell viability or barrier functions. A swelling degree study showed that alginate-chitosan hydrogel containing dextran-fluorescein isothiocyanate-labeled NPs collapsed in the colon. Once delivered, NPs quickly released KPV on or within the closed area of colonocytes. The inflammatory responses to lipopolysaccharide were reduced in Caco2-BBE (brush border enterocyte) cells exposed to NP-KPV compared with those exposed to NPs alone, in a dose-dependent fashion. Mice given dextran sodium sulfate (DSS) followed by NP-KPV were protected against inflammatory and histologic parameters, compared with mice given only DSS. CONCLUSIONS: Nanoparticles are a versatile drug delivery system that can overcome physiologic barriers and target anti-inflammatory agents such as the peptide KPV to inflamed areas. By using NPs, KPV can be delivered at a concentration that is 12,000-fold lower than that of KPV in free solution, but with similar therapeutic efficacy. Administration of encapsulated drug-loaded NPs is a novel therapeutic approach for IBD.
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