Departamento de Farmacia, Facultad de Farmacia, Universidad de Concepción, Concepción, Chile.
Int J Nanomedicine. 2013;8:2065-76. doi: 10.2147/IJN.S39327. Epub 2013 May 27.
In this work, microparticles were prepared by spray-drying using albumin, chondroitin sulfate, and hyaluronic acid as excipients to create a controlled-release methylprednisolone system for use in inflammatory disorders such as arthritis. Scanning electron microscopy demonstrated that these microparticles were almost spherical, with development of surface wrinkling as the methylprednisolone load in the formulation was increased. The methylprednisolone load also had a direct influence on the mean diameter and zeta potential of the microparticles. Interactions between formulation excipients and the active drug were evaluated by x-ray diffraction, differential scanning calorimetry, and thermal gravimetric analysis, showing limited amounts of methylprednisolone in a crystalline state in the loaded microparticles. The encapsulation efficiency of methylprednisolone was approximately 89% in all formulations. The rate of methylprednisolone release from the microparticles depended on the initial drug load in the formulation. In vitro cytotoxic evaluation using THP-1 cells showed that none of the formulations prepared triggered an inflammatory response on release of interleukin-1β, nor did they affect cellular viability, except for the 9.1% methylprednisolone formulation, which was the maximum test concentration used. The microparticles developed in this study have characteristics amenable to a therapeutic role in inflammatory pathology, such as arthritis.
在这项工作中,使用白蛋白、硫酸软骨素和透明质酸作为赋形剂通过喷雾干燥制备了微粒,以创建用于治疗关节炎等炎症性疾病的甲基强的松龙控制释放系统。扫描电子显微镜显示,这些微粒几乎呈球形,随着制剂中甲基强的松龙负载量的增加,表面出现皱纹。甲基强的松龙的负载量也直接影响微粒的平均直径和zeta 电位。通过 X 射线衍射、差示扫描量热法和热重分析评估制剂赋形剂与活性药物之间的相互作用,表明负载微粒中结晶状态的甲基强的松龙含量有限。所有配方中甲基强的松龙的包封效率约为 89%。微粒中甲基强的松龙的释放速率取决于制剂中初始药物的负载量。使用 THP-1 细胞进行的体外细胞毒性评估表明,除了使用的最大测试浓度 9.1%的甲基强的松龙配方外,所制备的制剂在释放白细胞介素-1β时均不会引发炎症反应,也不会影响细胞活力。本研究中开发的微粒具有在炎症性病理(如关节炎)中发挥治疗作用的特性。