College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-Gu, Gwangju 61186, Korea.
Int J Mol Sci. 2019 Jul 5;20(13):3312. doi: 10.3390/ijms20133312.
Methotrexate (MTX) is a folic acid antagonist used as an effective drug to treat various kinds of cancers. However, MTX has limited use in cancer chemotherapy due to its adverse effects such as poor bioavailability, low specificity, drug resistance, and dose-dependent side effects. To improve lymphatic delivery and reduce toxicity of MTX, MTX-loaded nanoparticles (NPs) were prepared in the present study. NPs were prepared with double emulsion solvent evaporation method using poly(lactide-co-glycolide) (PLGA). NPs were assessed for size, encapsulation efficiency, morphology, Fourier-transform infrared spectroscopy, X-ray diffraction, and thermal characterization. In vitro release profiles and cytotoxicity of these NPs were also evaluated. Prepared NPs and free MTX were administered orally or intravenously (5 mg/kg as MTX) to rats to evaluate their pharmacokinetic characteristics and lymphatic delivery effects. Mean particle size and encapsulation efficiency of NPs were 163.7 ± 10.25 nm and 93.3 ± 0.5%, respectively. Prepared NPs showed a sustained release profile of MTX in vitro and may be effective to cancer cells. Area under the blood concentration-time curve, total clearance, half-life, and lymphatic targeting efficiency were significantly different ( < 0.05) between prepared NPs and free MTX. These results demonstrate that MTX-loaded PLGA NPs are good candidates for targeted delivery of MTX to the lymphatic system.
甲氨蝶呤（MTX）是一种叶酸拮抗剂，可用作治疗各种癌症的有效药物。然而，由于其生物利用度低、特异性低、耐药性和剂量依赖性副作用等不良反应，MTX 在癌症化疗中的应用有限。为了提高 MTX 的淋巴递药效率并降低其毒性，本研究制备了载 MTX 的纳米粒（NPs）。采用聚（乳酸-共-乙醇酸）（PLGA）的双乳液溶剂蒸发法制备 NPs。对 NPs 的粒径、包封率、形态、傅里叶变换红外光谱、X 射线衍射和热特性进行了评估。还评价了这些 NPs 的体外释放曲线和细胞毒性。将制备的 NPs 和游离 MTX 经口或静脉内（以 MTX 计 5mg/kg）给予大鼠，以评估其药代动力学特征和淋巴递药效果。NPs 的平均粒径和包封率分别为 163.7±10.25nm 和 93.3±0.5%。制备的 NPs 在体外呈现出 MTX 的持续释放曲线，可能对癌细胞有效。AUC0-t、总清除率、半衰期和淋巴靶向效率在制备的 NPs 和游离 MTX 之间有显著差异（<0.05）。这些结果表明，载 MTX 的 PLGA NPs 是将 MTX 靶向递送至淋巴系统的良好候选物。
