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

• Published in: International journal of pharmaceutics Vol. 557; pp. 135 - 144
• Main Authors: Chen, Qiubing, Gou, Shuangquan, Ma, Panpan, Song, Heliang, Zhou, Xin, Huang, Yamei, Kwon Han, Moon, Wan, Ying, Kang, Yuejun, Xiao, Bo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25.02.2019
• Subjects: Curcumin; Drug accumulation; Oral administration; Porous nanoparticle; Ulcerative colitis; Porous nanoparticle; Curcumin; Drug accumulation; Oral administration; Ulcerative colitis
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2018.12.046

[Display omitted] 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-α) 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.