Oral administration of colitis tissue-accumulating porous nanoparticles for ulcerative colitis therapy

被引:48
作者
Chen, Qiubing [1 ]
Gou, Shuangquan [1 ]
Ma, Panpan [1 ,2 ]
Song, Heliang [3 ]
Zhou, Xin [1 ]
Huang, Yamei [1 ]
Han, Moon Kwon [3 ]
Wan, Ying [4 ]
Kang, Yuejun [1 ]
Xiao, Bo [1 ]
机构
[1] Southwest Univ, Fac Mat & Energy, Chongqing Key Lab Soft Matter Mat Chem & Funct Mf, Chongqing 400715, Peoples R China
[2] Guangdong Inst Med Instruments, Guangdong Key Lab Med Elect Instruments & Polymer, Natl Engn Res Ctr Healthcare Devices, Guangzhou 510500, Guangdong, Peoples R China
[3] Georgia State Univ, Ctr Diagnost & Therapeut, Atlanta, GA 30302 USA
[4] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
Oral administration; Drug accumulation; Porous nanoparticle; Curcumin; Ulcerative colitis; INFLAMMATORY-BOWEL-DISEASE; DRUG-DELIVERY; POLYMERIC NANOPARTICLES; GASTROINTESTINAL MUCUS; CURCUMIN; ACID; COMPONENT; RELEASE; BARRIER; TRACT;
D O I
10.1016/j.ijpharm.2018.12.046
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
To improve the penetration and accumulation of anti-inflammatory drugs in colitis tissue, we functionalized the surface of porous poly(lactic-co-glycolic acid) nanoparticles (NPs) using pluronic F127 (PF127) and loaded curcumin (CUR) into the resulting NPs to obtain porous PF127-functionalized CUR-loaded NPs (porous PF127-NPs). These NPs had an average hydrodynamic diameter of about 270 nm with a highly monodisperse size distribution, slightly negative surface charge and controllable CUR release profile. It was found that they had good biocompatibility and yielded a much higher cellular uptake rate of CUR than porous CUR-loaded NPs without PF127 modification (porous NPs). In addition, porous PF127-NPs showed a greater capacity to inhibit the major pro-inflammatory cytokines (IL-6, IL-12 and TNF-alpha) secreted from lipopolysaccharide-activated macrophages than porous NPs and non-porous PF127-NPs. In vivo experiments suggested that porous PF127-NPs achieved the best therapeutic outcomes against ulcerative colitis (UC) in mice compared with porous NPs and non-porous PF127-NPs. Our results clearly demonstrate that these fabricated porous PF127-NPs show a great promise as an efficient CUR nanocarrier for UC therapy.
引用
收藏
页码:135 / 144
页数:10
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