Abstract The primary aim of our study is to formulate the meloxicam loaded chitosan-magnetite nanoconjugates (MC-MNCs) for the magnetically targeted rheumatoid arthritis therapy with an anticipation to improve the drug efficacy through enhancing its regional bioavailability, reducing dose frequency and related toxicity. The chitosan-magnetite nanoconjugates was prepared by in-situ co-precipitation of FeSO4 and FeCl3 solution in basic medium subsequently cross-linked with chitosan in the presence of sodium tripolyphosphate. Meloxicam dispersion was co-loaded onto the chitosan-magnetite nanoconjugates yielding MC-MNCs. These nanoconjugates were characterized by diverse techniques for their morphological, physicochemical, magnetic, pharmaceutical and pharmacological properties. MC-MNCs were roughly spherical. DLS measurements confirm its mean hydrodynamic size (258 nm), polydispersity index (0.233) and zeta potential (25.6 mV). FT-IR spectroscopic investigations showed the functional integrity of meloxicam, while XRD measurements showed the crystalline nature of magnetite and meloxicam in MC-MNCs, respectively. The chitosan-coated magnetite nanoparticles (C-MNP) and MC-MNCs showed a magnetic susceptibility of 168 X 10-5 and 110 X 10-5 SI units, respectively. The encapsulation efficiency and loading capacity of meloxicam entrapped into MC-MNCs was found to be 82% and 13% respectively. The in-vitro meloxicam release in phosphate buffer saline (pH 7.4) showed an initial burst release effect and followed by a slow drug release pattern. Meloxicam release from the MC-MNCs followed the Michaelis-Menten kinetics, adopting a super case II transport mechanism. MC-MNCs was found sufficiently stable with no major visual changes. Murine models of inflammation and arthritis was used to test the pharmacological efficacy of MC-MNCs. Magnetically targeted drug delivery of MC-MNCs enhanced the anti-inflammatory effect and anti-arthritic activity on the carrageenan-induced paw oedema in adjuvant-induced arthritis models in rats when compared with other treatments without applied magnetic field. Considering the overall research analysis, it is concluded that the MC-MNCs could be used as a viable alternative to the conventional formulations of meloxicam to ease rheumatoid arthritis.

中文翻译：

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开发针对类风湿性关节炎关节的美洛昔康-壳聚糖磁性纳米缀合物：药物表征和小鼠模型的临床前评估

摘要 我们研究的主要目的是配制用于磁性靶向类风湿性关节炎治疗的美洛昔康负载壳聚糖-磁铁矿纳米偶联物（MC-MNCs），以期通过提高其区域生物利用度、降低剂量频率和相关毒性来提高药物疗效。通过 FeSO4 和 FeCl3 溶液在碱性介质中的原位共沉淀，随后在三聚磷酸钠的存在下与壳聚糖交联，制备壳聚糖-磁铁矿纳米复合物。美洛昔康分散体共负载到壳聚糖-磁铁矿纳米缀合物上，产生 MC-MNC。这些纳米缀合物的特征在于其形态学、物理化学、磁性、药物和药理学特性的多种技术。MC-MNCs 大致呈球形。DLS 测量证实了其平均流体动力学尺寸 (258 nm)、多分散指数 (0.233) 和 zeta 电位 (25.6 mV)。FT-IR 光谱研究显示了美洛昔康的功能完整性，而 XRD 测量显示了磁铁矿和美洛昔康在 MC-MNCs 中的结晶性质。壳聚糖包覆的磁铁矿纳米粒子 (C-MNP) 和 MC-MNCs 的磁化率分别为 168 X 10-5 和 110 X 10-5 SI 单位。发现包裹在 MC-MNCs 中的美洛昔康的包封率和负载能力分别为 82% 和 13%。在磷酸盐缓冲盐水 (pH 7.4) 中的体外美洛昔康释放显示出初始突释效应，然后是缓慢的药物释放模式。MC-MNCs 的美洛昔康释放遵循 Michaelis-Menten 动力学，采用超级案例 II 转运机制。发现 MC-MNCs 足够稳定，没有重大的视觉变化。炎症和关节炎的小鼠模型用于测试 MC-MNCs 的药理功效。与未施加磁场的其他治疗相比，MC-MNCs 的磁性靶向药物递送增强了对角叉菜胶诱导的大鼠爪水肿的抗炎作用和抗关节炎活性。考虑到整体研究分析，得出的结论是，MC-MNCs 可用作美洛昔康常规制剂的可行替代品，以缓解类风湿性关节炎。与未施加磁场的其他治疗相比，MC-MNCs 的磁性靶向药物递送增强了对角叉菜胶诱导的大鼠爪水肿的抗炎作用和抗关节炎活性。考虑到整体研究分析，得出的结论是，MC-MNCs 可用作美洛昔康常规制剂的可行替代品，以缓解类风湿性关节炎。与未施加磁场的其他治疗相比，MC-MNCs 的磁性靶向药物递送增强了对角叉菜胶诱导的大鼠爪水肿的抗炎作用和抗关节炎活性。考虑到整体研究分析，得出的结论是，MC-MNCs 可用作美洛昔康常规制剂的可行替代品，以缓解类风湿性关节炎。