Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model.
Laroui. Hamed H; Dalmasso. Guillaume G; Nguyen. Hang Thi Thu HT; Yan. Yutao Y; Sitaraman. Shanthi V SV; Merlin. Didier D
Key Findings
- Nanoparticles (â400â¯nm) loaded with KPV can be encapsulated in an alginateâchitosan hydrogel that collapses in the colon, releasing the peptide at the site of inflammation.
- In cultured colon cells, the NPâKPV reduced inflammatory responses to lipopolysaccharide in a doseâdependent way without harming cell viability.
- Mice given the NPâKPV after inducing colitis with dextran sodium sulfate showed significantly less inflammation and tissue damage compared with untreated mice.
- The therapeutic effect was achieved with a KPV dose about 12,000âfold lower than the dose needed when the peptide is given in free solution.
Practical Outcomes
- For now, this research is a proofâofâconcept that ultraâlow doses of KPV could work if delivered directly to the colon, but the nanoparticleâhydrogel system is not something you can make at home. It suggests that future gutâtargeted supplements might be far more potent than current oral peptides, but more development and human trials are needed before any DIY protocol is safe or effective.
Summary
Scientists built tiny particles that carry the antiâinflammatory peptide KPV and hide them inside a special gel that only breaks down in the colon. In mice with chemicallyâinduced colitis, this system released the peptide right where the gut is inflamed and dramatically cut down inflammation, even though the amount of KPV used was 12,000 times lower than if you just gave the free peptide.
Abstract
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. 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. 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. 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.
Study Information
pubmed
2009
2009-11-10T00:00:00.000Z
10.1053/j.gastro.2009.11.003
232
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