Oral IL-10 gene delivery in a microsphere-based formulation for local transfection and therapeutic efficacy in inflammatory bowel disease.
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-gamma, TNF-alpha, IL-1alpha, IL-1beta 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.
Bhavsar
M D
MD
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02115-5005, USA.
Amiji
M M
MM
D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005780:Gelatin; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D023421:Models, Animal; D053758:Nanoparticles; D009195:Peroxidase / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods*; D019076:Transgenes; D014302:Trinitrobenzenesulfonic Acid
D015415:Biomarkers; D016753:Interleukin-10; D014302:Trinitrobenzenesulfonic Acid; D005780:Gelatin; D009195:Peroxidase