Sangi Sibghatullah, SreeHarsha Nagaraja, Bawadekji Abdulhakim, Al Ali Mouhanad
Department of Clinical Pharmacy, Faculty of Pharmacy, Northern Border University, Rafha, Saudi Arabia,
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia.
Drug Des Devel Ther. 2018 Sep 18;12:3051-3060. doi: 10.2147/DDDT.S173485. eCollection 2018.
Currently, microsphere technology plays a major role in the development of many new cancer therapies. In the current study, we proposed a targeted drug-delivery system to improve the treatment efficacy of one of the common conventional chemotherapeutic drugs used to treat lung tumors, 5-fluorouracil (5-FU).
Following the preparation and optimization of small, solid micro-spheres, ranging in diameter between 5 and 15 µm, the final product 5-fluorouracil gelatin (5-FUG) was formulated using a Buchi Nano Spray Dryer by varying the drug:polymer ratio.
Particle yield was calculated as 65% ± 1.2%, and the drug content in the formulation was recorded as 74% ± 1.6%. Particle surface morphology was examined as shriveled shape (crumpled/folded); particle size distribution displayed a binomial distribution, with a mean diameter of 9.6 µm. In vitro drug release studies revealed that ~36.4% of the 5-FU in 5-FUG was released in the first hour after injection. Clinically, this would lead to initial or burst release, facilitating a quick rise to therapeutic levels. In contrast to the pure 5-FU drug (89.2% of the drug released in the first 30 minutes), 99.1% of the drug in 5-FUG was released from the spray-dried particles for a period of 12 hours. A two-compartment model was used to generate plasma concentration-time curves. 5-FUG injection has a much different distribution in vivo in contrast to intravenous injection of 5-FU. In addition, the half-life after intravenous injection of 5-FUG, () = 1.23 hours and () = 18.3 hours, was considerably longer than that of 5-FU, () = 0.34 hours and () = 8.62 hours. Examination of stained lung tissue sections showed no histopathological tissue changes or evidence of gross pathology. In addition, the optimized formulation demonstrated an increased stability under both long-term and refrigerated storage conditions.
Our goal was to develop similar delivery systems for other chemotherapeutic drugs that are site specific to different disease models/tumor types.
目前，微球技术在许多新型癌症治疗方法的开发中发挥着重要作用。在本研究中，我们提出了一种靶向给药系统，以提高用于治疗肺部肿瘤的常见传统化疗药物之一5-氟尿嘧啶（5-FU）的治疗效果。
在制备并优化直径为5至15微米的小型固体微球后，使用布奇纳米喷雾干燥器通过改变药物与聚合物的比例来配制最终产品5-氟尿嘧啶明胶（5-FUG）。
颗粒产率计算为65%±1.2%，制剂中的药物含量记录为74%±1.6%。颗粒表面形态检查为皱缩形状（皱巴巴/折叠状）；粒度分布呈二项分布，平均直径为9.6微米。体外药物释放研究表明，注射后第一小时内5-FUG中约36.4%的5-FU被释放。在临床上，这将导致初始或突释，有助于迅速达到治疗水平。与纯5-FU药物（在前30分钟内89.2%的药物被释放）相比，5-FUG中99.1%的药物在12小时内从喷雾干燥颗粒中释放。使用二室模型生成血浆浓度-时间曲线。与静脉注射5-FU相比，5-FUG注射在体内的分布有很大不同。此外，静脉注射5-FUG后的半衰期（）=1.23小时和（）=18.3小时，明显长于5-FU的半衰期（）=0.34小时和（）=8.62小时。对染色的肺组织切片检查显示没有组织病理学组织变化或大体病理学证据。此外，优化后的制剂在长期和冷藏储存条件下均表现出更高的稳定性。
我们的目标是为其他针对不同疾病模型/肿瘤类型具有位点特异性的化疗药物开发类似的给药系统。
