Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Molecular and Medical Research (MMR) Strategic Research Centre, Faculty of Health, Technology Precinct (GTP), Deakin University, Waurn Ponds, Victoria 3216, Australia.
Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Molecular and Medical Research (MMR) Strategic Research Centre, Faculty of Health, Technology Precinct (GTP), Deakin University, Waurn Ponds, Victoria 3216, Australia.
Biomaterials. 2014 Aug;35(26):7522-34. doi: 10.1016/j.biomaterials.2014.04.109. Epub 2014 Jun 3.
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-Fe-bLf-NCs) were examined in in vitro inflammatory OA model and in collagen-induced arthritis (CIA) mice. By diminishing IL-1β 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-1β, NO, JNK 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.
骨关节炎 (OA) 的治疗方法存在重大局限性，包括全身毒性、关节保留减少以及无法抑制疾病进展。在这项研究中，研究人员研究了 100%铁饱和牛乳铁蛋白包封在藻酸盐-壳聚糖聚合物纳米载体（AEC-CP-Fe-bLf-NCs）中的治疗潜力，这种纳米载体在体外炎症性 OA 模型和胶原诱导性关节炎（CIA）小鼠中进行了研究。与空白和 C-CP-Apo（无金属）-bLf-NCs 相比，C-CP-Fe-bLf-NCs 通过减少 IL-1β 诱导的凋亡和氧化应激，上调了软骨细胞的保护和增殖。与空白和 C-CP-Apo（无金属）-bLf-NCs 相比，纳米载体在小鼠中的口服给药是无毒的，它通过减少关节炎症和显著下调分解代谢基因、IL-1β、NO、JNK 和 MAPK 的表达，显著诱导疾病修饰活性。此外，在 AEC-CP-Fe-bLf-NCs 治疗的小鼠中，通过抑制铁转运受体的 miRNA，上调了 II 型胶原蛋白、聚集蛋白和炎症耗竭的铁和钙代谢。此外，AEC-CP-Fe-bLf-NCs 溶解了小鼠关节中发现的焦磷酸钙晶体，这表明纳米配方的 Fe-bLf 具有重要的治疗能力，可用于治疗慢性炎症性风湿性疾病，如 OA。
