The effect of oral administration of iron saturated-bovine lactoferrin encapsulated chitosan-nanocarriers on osteoarthritis

被引:61
|
作者
Samarasinghe, Rasika M. [1 ]
Kanwar, Rupinder K. [1 ]
Kanwar, Jagat R. [1 ]
机构
[1] Deakin Univ, Mol & Med Res MMR Strateg Res Ctr, NLIMBR, SoM,Fac Hlth,Technol Precinct GTP, Waurn Ponds, Vic 3216, Australia
基金
英国医学研究理事会;
关键词
Nanocarriers; Osteoarthritis; Chitosan; Iron metabolism; miRNA; Lactoferrin; ANTIOXIDANT ENZYME-ACTIVITIES; GUT EPITHELIAL-CELLS; ARTICULAR-CARTILAGE; RHEUMATOID-ARTHRITIS; OXIDATIVE STRESS; CANCER-CHEMOTHERAPY; IN-VITRO; CALCIUM; METABOLISM; REGULATOR;
D O I
10.1016/j.biomaterials.2014.04.109
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页码:7522 / 7534
页数:13
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