Theranostics 2016; 6(12):2250-2266. doi:10.7150/thno.15710

Research Paper

Combination Therapy for Ulcerative Colitis: Orally Targeted Nanoparticles Prevent Mucosal Damage and Relieve Inflammation

Bo Xiao1,2✉, Zhan Zhang2, Emilie Viennois2,3, Yuejun Kang1, Mingzhen Zhang2, Moon Kwon Han2, Jiucun Chen1, Didier Merlin2,3

1. Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing, 400715, P. R. China.
2. Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, 30302, USA.
3. Atlanta Veterans Affairs Medical Center, Decatur, 30033, USA.

Abstract

Combination therapy is an emerging strategy that is under intensive preclinical investigation for the treatment of various diseases. CD98 is highly overexpressed on the surfaces of epithelial cells and macrophages in the colon tissue with ulcerative colitis (UC), which is usually associated with mucosal damage and inflammation. We previously proved that CD98 siRNA (siCD98)-induced down-regulation of CD98 in colitis tissue decreased the severity of UC to a certain extent. In an effort to further improve the therapeutic efficacy, we aim to simultaneously deliver siCD98 in combination with a potent anti-inflammatory agent, curcumin (CUR), using hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant spherical HA-siCD98/CUR-NPs are featured by a desirable particle size (∼246 nm) and slightly negative zeta potential (∼-14 mV). The NPs functionalized with HA are able to guide the co-delivery of drugs to the targeted cells related to UC therapy (colonic epithelial cells and macrophages). Compared to either siCD98- or CUR-based monotherapy, co-delivery of siCD98 and CUR by HA-functionalized NPs can exert combinational effects against UC by protecting the mucosal layer and alleviating inflammation both in vitro and in vivo. This study shows the promising capability of the co-delivered siCD98 and CUR for boosting the conventional monotherapy via this novel nanotherapeutic agent, which offers a structurally simple platform for orally administered delivery of drugs to target cells in UC therapy.

Keywords: oral administration, combination therapy, mucosal protection, anti-inflammation, targeted nanoparticle, ulcerative colitis.

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How to cite this article:
Xiao B, Zhang Z, Viennois E, Kang Y, Zhang M, Han MK, Chen J, Merlin D. Combination Therapy for Ulcerative Colitis: Orally Targeted Nanoparticles Prevent Mucosal Damage and Relieve Inflammation. Theranostics 2016; 6(12):2250-2266. doi:10.7150/thno.15710. Available from http://www.thno.org/v06p2250.htm