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

Combination Therapy for Ulcerative Colitis: Orally Targeted Nanoparticles Prevent Mucosal Damage and Relieve Inflammation.
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溃疡性结肠炎的联合疗法:口服靶向纳米颗粒可预防粘膜损伤并缓解炎症

DOI:
10.7150/thno.15710
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发表时间:
2016
期刊:
影响因子:
12.4
通讯作者:
Merlin D
Merlin D
中科院分区:
医学1区
文献类型:
--
作者:
Xiao B;Zhang Z;Viennois E;Kang Y;Zhang M;Han MK;Chen J;Merlin D

文献摘要

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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.