Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Int J Pharm. 2018 Apr 5;540(1-2):89-97. doi: 10.1016/j.ijpharm.2018.01.039. Epub 2018 Jan 31.
Celecoxib (CLX) is a selective COX-2 inhibitor with anticancer potential in a COX-2 dependent and independent manner. CLX's low water solubility has a dose limiting effect on its utilization in cancer treatment. Here, we developed liposomal drug delivery systems to allow a systemic administration and increase tumor accumulation of CLX based on the enhanced permeability and retention (EPR) mechanism. Nine liposomal formulations has been prepared with different phospholipid compositions; among them three sets of liposomal formulations were selected based on characterization and stability for further studies. Anti-tumor effects of CLX-entrapped liposomal formulations were tested in vitro by cytotoxicity test and in vivo in BALB/c mice bearing C26 colon carcinoma. Biodistribution of liposomal-CLX has been studied by radiolabeling of CLX with I.The selected formulations had average size of about 100 nm, a narrow monomodal distribution with storage stability of at least one year at 4 °C. The HSPC/DSPG/cholesterol/DSPE-PEG2000/CLX (65/10/10/5/10 M ratio) liposomal formulation had slowest release profile and greatest antitumor effects in vivo. This liposomal ICLX formulation had a three times more accumulation in tumor site in comparison to the free ICLX. Liposomal CLX may serve as a safe, slow release and effective anti-tumor agent and merits further investigation.
塞来昔布（CLX）是一种选择性 COX-2 抑制剂，具有 COX-2 依赖性和非依赖性的抗癌潜力。CLX 的低水溶性对其在癌症治疗中的应用有剂量限制作用。在这里，我们开发了基于增强的通透性和保留（EPR）机制的脂质体药物递送系统，允许系统给药并增加 CLX 的肿瘤积累。已经制备了 9 种不同磷脂组成的脂质体配方; 其中，根据表征和稳定性选择了三组脂质体配方进行进一步研究。通过体外细胞毒性试验和体内 BALB/c 小鼠 C26 结肠癌细胞模型研究了 CLX 包封的脂质体制剂的抗肿瘤作用。通过用 I 对 CLX 进行放射性标记研究了脂质体-CLX 的体内分布。所选配方的平均粒径约为 100nm，具有窄单模态分布，在 4°C 下至少稳定一年。HSPC/DSPG/胆固醇/DSPE-PEG2000/CLX（65/10/10/5/10M 比例）脂质体配方具有最慢的释放曲线和最强的体内抗肿瘤作用。与游离 ICLX 相比，这种脂质体 ICLX 制剂在肿瘤部位的积累增加了三倍。脂质体 CLX 可能是一种安全、缓释和有效的抗肿瘤药物，值得进一步研究。
