Abstract：
Inflammatory diseases including rheumatoid arthritis are major health problems. Although different techniques and drugs are clinically available for the diagnosis and therapy of the disease, novel approaches regarding radiolabeled drug delivery systems are researched. Hence, in the present study, it was aimed to design, prepare, and characterize 99mTc-radiolabeled and tofacitinib citrate-encapsulated microsphere loaded poloxamer in situ gel formulations for the intra-articular treatment. Among nine different microsphere formulations, MS/TOFA-9 was chosen as the most proper one due to particle size, high encapsulation efficiency, and in vitro drug release behavior. Poloxamer 338 at a concentration of 15% was used to prepare in situ gel formulations. For intra-articular administration, microspheres were dispersed in an in situ gel containing 15% Poloxamer 338 and characterized in terms of gelation temperature, viscosity, rheological, mechanical, and spreadability properties. After the determination of the safe dose for MS/TOFA-9 and PLX-MS/TOFA-9 as 40 µL/mL in the cell culture study performed on healthy cells, the high anti-inflammatory effects were due to significant cellular inhibition of fibroblasts. In the radiolabeling studies with 99mTc, the optimum radiolabeling condition was determined as 200 ppm SnCl2 and 0.5 mg ascorbic acid, and both 99mTc-MS/TOFA-9 and 99mTc-PLX-MS/TOFA-9 exhibited high cellular binding capacity. In conclusion, although further in vivo experiments are required, PLX-MS/TOFA-9 was found to be a promising agent for intra-articular injection in rheumatoid arthritis.
摘要：
包括类风湿性关节炎在内的炎性疾病是主要的健康问题。尽管临床上有不同的技术和药物用于该疾病的诊断和治疗，研究了关于放射性标记药物递送系统的新方法。因此，在本研究中，它的目的是设计，准备,并表征99mTc-放射性标记和托法替尼柠檬酸盐包封的微球负载泊洛沙姆原位凝胶制剂用于关节内治疗。在九种不同的微球配方中，MS/TOFA-9因粒度而被选择为最合适的，封装效率高，和体外药物释放行为。使用浓度为15%的泊洛沙姆338制备原位凝胶制剂。对于关节内给药，微球分散在含有15%泊洛沙姆338的原位凝胶中，并以凝胶化温度为特征，粘度,流变学,机械,和铺展性属性。在对健康细胞进行的细胞培养研究中，确定MS/TOFA-9和PLX-MS/TOFA-9的安全剂量为40µL/mL后，高抗炎作用是由于成纤维细胞的显着细胞抑制。在99mTc的放射性标记研究中，最佳放射性标记条件确定为200ppmSnCl2和0.5mg抗坏血酸，99mTc-MS/TOFA-9和99mTc-PLX-MS/TOFA-9均表现出高细胞结合能力。总之,尽管需要进一步的体内实验，PLX-MS/TOFA-9被发现是用于类风湿性关节炎关节内注射的有前途的药物。
