Journal
MOLECULAR THERAPY
Volume 25, Issue 7, Pages 1628-1640Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2016.11.020
Keywords
-
Categories
Funding
- Department of Veterans Affairs [BX002526]
- National Institutes of Health of Diabetes and Digestive and Kidney [RO1-DK-071594]
- National Natural Science Foundation of China [51503172, 81571807]
- Fundamental Research Funds for the Central Universities [SWU114086, XDJK2015C067]
- Basic and Frontier Research Project of Chongqing [cstc2016jcyjA0078]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars (State Education Ministry)
- Department of Veterans Affairs
Ask authors/readers for more resources
Overcoming adverse effects and selectively delivering drug to target cells are two major challenges in the treatment of ulcerative colitis (UC). Lysine-proline-valine (KPV), a naturally occurring tripeptide, has been shown to attenuate the inflammatory responses of colonic cells. Here, we loaded KPV into hyaluronic acid (HA)-functionalired polymeric nanoparticles (NPs). The resultant HA-KPV-NPs had a desirable particle size (similar to 272.3 nm) and a slightly negative zeta potential similar to-5.3 mV). These NPs successfully mediated the targeted delivery of KPV to key UC therapy-related cells (colonic epithelial cells and macrophages). In addition, these KPV-loaded NPs appear to be nontoxic and biocompatible with intestinal cells. Intriguingly, we found that HA-KPV-NPs exert combined effects against UC by both accelerating mucosal healing and alleviating inflammation. Oral administration of HA-KPV-NPs encapsulated in a hydrogel (chitosan/alginate) exhibited a much stronger capacity to prevent mucosa damage and down regulate TNF-alpha, thus they showed a much better therapeutic efficacy against UC in a mouse model, compared with a KPV-NP/hydrogel system. These results collectively demonstrate that our HA-KPV-NP/hydrogel system has the capacity to release HA-KPV-NPs in the colonic lumen and that these NPs subsequently penetrate into colitis tissues and enable KPV to be internalized into target cells, thereby alleviating UC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available