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Oral IL-10 gene delivery in a microsphere-based formulation for local transfection and therapeutic efficacy in inflammatory bowel disease

Gene Therapy volume 15, pages 1200–1209 (2008)Cite this article

Abstract

The objective of this study was to examine the potential of oral interleukin-10 (IL-10) gene therapy for the treatment of inflammatory bowel disease (IBD). Nanoparticles-in-microsphere oral system (NiMOS) was formulated with murine IL-10-expressing plasmid DNA in type-B gelatin nanoparticles, which were further encapsulated in poly(epsilon-caprolactone) microsphere matrix. Upon oral administration in an acute colitis model, IL-10 expression in the large intestine was measured by quantitative real-time PCR and ELISA. The locally expressed IL-10 was able to suppress the levels of proinflammatory cytokines, such as IFN-γ, TNF-α, IL-1α, IL-1β and IL-12, as well as certain chemokines. The therapeutic benefits of transfected IL-10 were further demonstrated by an increase in body weight, favorable clinical activity score, restoration in colon length and weight, and suppression of inflammatory response as assessed by tissue histological analysis and myeloperoxidase activity. The results of this study provide highly encouraging evidence of oral gene delivery and transfection and potential utility in IBD therapy.

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Acknowledgements

We are grateful to David Nyugen in Professor Robert Langer's laboratory at MIT (Cambridge, MA, USA) for the use the Coulter particle size analysis instrument. Dr Takeshi Sano and Dr Alan Jerusalmi from the Beth Israel Deaconess Medical Center (Boston, MA, USA) are acknowledged for providing technical assistance with the development of murine acute colitis model.

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  1. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, USA

    M D Bhavsar & M M Amiji

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  1. M D Bhavsar
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  2. M M Amiji
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Correspondence to M M Amiji.

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Bhavsar, M., Amiji, M. Oral IL-10 gene delivery in a microsphere-based formulation for local transfection and therapeutic efficacy in inflammatory bowel disease. Gene Ther 15, 1200–1209 (2008). https://doi.org/10.1038/gt.2008.67

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