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Lakshadi Guggul在新型海藻酸盐包裹的壳聚糖磷酸钙纳米载体中的抗关节炎和软骨保护活性。

Antiarthritic and chondroprotective activity of Lakshadi Guggul in novel alginate-enclosed chitosan calcium phosphate nanocarriers.

作者信息

Samarasinghe Rasika M, Kanwar Rupinder K, Kumar Kuldeep, Kanwar Jagat R

机构信息

Nanomedicine-Laboratory of Immunology & Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Molecular & Medical Research (MMR) Strategic Research Centre, Faculty of Health, Technology Precinct (GTP), Deakin University, Waurn Ponds, Victoria 3217, Australia.

出版信息

Nanomedicine (Lond). 2014 May;9(6):819-37. doi: 10.2217/nnm.13.219. Epub 2014 Jan 9.

Abstract

AIM

This study aimed to evaluate the antiarthritic and chondroprotective potentials of Lakshadi Guggul (LG) and Cissus quadrangularis encapsulated in novel alginate-enclosed chitosan-calcium phosphate nanocarriers (NCs) both in vitro in primary human chondrocytes and in vivo in mice with collagen-induced arthritis.

MATERIALS & METHODS: Chondrocytes exposed to IL-1β and osteoarthritis chondrocytes grown in an ex vivo inflammation-based coculture were incubated with different concentrations of herbals, and cell modulatory activities were determined. For in vivo studies, herbals and their encapsulated nanoformulations were administered orally to DBA/1 mice with collagen-induced arthritis.

RESULTS

C. quadrangularis and LG showed enhanced chondroprotective and proliferative activity in IL-1β-exposed primary chondrocytes, with LG showing the highest therapeutic potency. LG increased viability, proliferative and mitogenic activity, and inhibited cell apoptosis and mitochondrial depolarization. In vivo studies with LG and alginate-enclosed chitosan-calcium phosphate LG NCs revealed cartilage regenerative activity in those administered with the nanoformulation. The NCs were nontoxic to mice, reduced joint swelling and paw volume, and inhibited gene expression of MMPs and cytokines.

CONCLUSION

The promising results from this study reveal, for the first time, the novel polymeric NC encapsulating LG as a potential therapeutic for rheumatic diseases.

摘要

目的

本研究旨在评估包裹于新型海藻酸盐包封的壳聚糖 - 磷酸钙纳米载体(NCs)中的拉克沙迪古古尔(LG)和四角金虎尾在原代人软骨细胞体外实验以及胶原诱导性关节炎小鼠体内实验中的抗关节炎和软骨保护潜力。

材料与方法

将暴露于白细胞介素 -1β的软骨细胞以及在基于体外炎症的共培养中生长的骨关节炎软骨细胞与不同浓度的草药一起孵育,并测定细胞调节活性。对于体内研究,将草药及其包裹的纳米制剂口服给予胶原诱导性关节炎的DBA/1小鼠。

结果

四角金虎尾和LG在暴露于白细胞介素 -1β的原代软骨细胞中显示出增强的软骨保护和增殖活性,其中LG显示出最高的治疗效力。LG提高了细胞活力、增殖和促有丝分裂活性,并抑制细胞凋亡和线粒体去极化。对LG和海藻酸盐包封的壳聚糖 - 磷酸钙LG NCs进行的体内研究表明,给予纳米制剂的小鼠具有软骨再生活性。这些NCs对小鼠无毒,减少了关节肿胀和爪体积,并抑制了基质金属蛋白酶和细胞因子的基因表达。

结论

本研究的有前景结果首次揭示了包裹LG的新型聚合物NC作为风湿性疾病潜在治疗方法的可能性。

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