Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Punjab 160 062, India.
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Punjab 160 062, India.
Int J Pharm. 2019 Feb 25;557:86-96. doi: 10.1016/j.ijpharm.2018.12.043. Epub 2018 Dec 22.
In an attempt to prepare novel core shell nanocapsules, lipid and Stearic acid-Valine conjugate (Biosurfactant) based nanosystem was prepared to attain high drug loading of hydrophilic drug methotrexate (MTX), with sustained release. Antisolvent nanoprecipitation technique was employed for the formulation of nanoparticles (NPs). Optimized formulation depicted 209.6 ± 31.3 nm particle size, 0.209 ± 0.072 PDI and 14.98 ± 1.33 %w/w drug loading. In vitro release depicted biphasic release for 12 h with initial burst phase followed by sustained release phase. In vitro Haemolytic study on RBCs revealed haemocompatible nature of MTX-Biosurfactant NPs compared to Biotrexate® (Zydus). In vitro cell culture studies showed 3.33 folds and 3.50 folds increase in cellular uptake of MTX at 10 µg/ml and 15 µg/ml concentration respectively for developed nanoparticles with 4.16 folds decrease in IC value. Higher apoptosis and increased lysosomal membrane permeability were obtained in MTX-Biosurfactants NPs. AUC and T was found to increase by 2.55 and 3.25 folds respectively in pharmacokinetic study. Significant reduction in tumor burden and serum toxicity marker level depicted efficacy and safety respectively of the formulation as compared to Biotrexate®. RBCs morphology was retained after MTX-Biosurfactants NPs exposure proving its haemocompatibility in vivo.
为了制备新型核壳纳米胶囊，我们制备了基于脂质和硬脂酸-缬氨酸缀合物（生物表面活性剂）的纳米系统，以实现亲水性药物甲氨蝶呤（MTX）的高载药量和持续释放。反溶剂纳米沉淀技术用于制备纳米颗粒（NPs）。优化的配方显示出 209.6±31.3nm 的粒径、0.209±0.072 的 PDI 和 14.98±1.33%w/w 的载药量。体外释放显示出 12 小时的双相释放，初始突释阶段后是持续释放阶段。对 RBC 的体外溶血研究表明，与 Biotrexate®（Zydus）相比，MTX-生物表面活性剂 NPs 具有血液相容性。体外细胞培养研究表明，在 10µg/ml 和 15µg/ml 浓度下，开发的纳米颗粒分别使 MTX 的细胞摄取增加了 3.33 倍和 3.50 倍，而 IC 值降低了 4.16 倍。在 MTX-生物表面活性剂 NPs 中观察到更高的细胞凋亡和溶酶体膜通透性增加。药代动力学研究发现 AUC 和 T 分别增加了 2.55 倍和 3.25 倍。与 Biotrexate®相比，制剂在肿瘤负担和血清毒性标志物水平方面的显著降低分别表明了其疗效和安全性。MTX-生物表面活性剂 NPs 暴露后 RBC 形态保持不变，证明其体内血液相容性。
