期刊
BIOMATERIALS
卷 35, 期 26, 页码 7522-7534出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.04.109
关键词
Nanocarriers; Osteoarthritis; Chitosan; Iron metabolism; miRNA; Lactoferrin
资金
- Australia-India Strategic Research Fund (AISRF)
- National Health and Medical Research Council (NHMRC)
Osteoarthritis (OA) treatments have major limitations which include systemic toxicity, reduced joint retention and inability to inhibit disease progression. In this study, the therapeutic potentials of 100% iron saturated-bovine lactoferrin encapsulated in alginate-chitosan polymeric nanocarriers (AEC-CP-FebLf-NCs) were examined in in vitro inflammatory OA model and in collagen-induced arthritis (CIA) mice. By diminishing IL-113 induced apoptotic and oxidative stress, chondrocyte protection and proliferation was up-regulated with C-CP-Fe-bLf-NCs as compared to void and C-CP-Apo(metal free)-bLf-NCs. Oral administration of nanocarriers in mice was non-toxic and it significantly induced disease modifying activity by reducing joint inflammation and significantly downregulating the expression of catabolic genes, IL-113, NO, JINK and MAPK. In addition, up-regulation of type II collagen, aggrecan and inflammation depleted iron and calcium metabolisms via inhibition of miRNA of iron transporting receptors was shown in AEC-CP-Fe-bLf-NCs treated mice. In addition, AEC-CP-Fe-bLf-NCs dissoluted calcium pyrophosphate crystals found in mice joints indicating the significantly important therapeutic ability of nanoformulated Fe-bLf to be utilized in the treatment of chronic inflammatory rheumatic diseases such as OA. 2014 Elsevier Ltd. All rights reserved.
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