Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 52, Issue -, Pages 157-164Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2019.04.030
Keywords
Oral administration; Mucus penetration; Nanoparticle; Curcumin; Ulcerative colitis
Categories
Funding
- National Natural Science Foundation of China [51503172, 81571807]
- Young Core Teacher Program of the Municipal Higher Educational Institution of Chongqing
- Venture and Innovation Support Program for Chongqing Overseas Returnees [cx2018029]
- Graduate Student Research Innovation [CYS18108]
- State Key Laboratory of Silkworm Genome Biology
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Oral nanotherapeutics have been proven to have great potential in the treatment of ulcerative colitis (UC). However, their therapeutic efficacies are mainly restricted by the lack of mucus-penetrating capacity. To overcome this obstacle, we functionalized the surface of curcumin (CUR)-loaded polymeric nanoparticles (NPs) with various amounts of pluronic F127 (PF127). The obtained NPs (NPs-I, NPs-II, NPs-III and NPs-IV) had hydrodynamic particle sizes around 250 nm with highly monodisperse size distributions, negatively charged surfaces and constant CUR release properties. It was found that the functionalization with PF127 notably improved the mucus-penetrating ability of NPs. Further cell experiments revealed that they showed negative cytotoxicities, and PF127-functionalized NPs (NPs-II, NPs-III and NPs-IV) yielded remarkably higher internalization rates of CUR in macrophages as compared to NPs without PF127 modification (NPs-I). Interestingly, NPs-III exhibited notably stronger capacity to decrease the secretion of TNF-alpha from macrophages when they were compared with other NPs. Finally, mouse experiments demonstrated that NPs-III achieved the best therapeutic efficacy against UC among all the tested NPs. Our results clearly suggest that PF127-functionalized polymeric NPs with desirable compositional proportions are promising and efficient nanotherapeutics for UC therapy.
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