Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey; Neuroscience Research Lab, Research Center for Translational Medicine, Koҫ University, Istanbul, Turkey.
Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey; Neuroscience Center and Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
J Control Release. 2017 Sep 10;261:187-198. doi: 10.1016/j.jconrel.2017.06.032. Epub 2017 Jul 3.
New drug delivery systems are highly needed in research and clinical area to effectively treat gliomas by reaching a high antineoplastic drug concentration at the target site without damaging healthy tissues. Intranasal (IN) administration, an alternative route for non-invasive drug delivery to the brain, bypasses the blood-brain-barrier (BBB) and eliminates systemic side effects. This study evaluated the antitumor efficacy of farnesylthiosalicylic acid (FTA) loaded (lipid-cationic) lipid-PEG-PLGA hybrid nanoparticles (HNPs) after IN application in rats. FTA loaded HNPs were prepared, characterized and evaluated for cytotoxicity. Rat glioma 2 (RG2) cells were implanted unilaterally into the right striatum of female Wistar rats. 10days later, glioma bearing rats received either no treatment, or 5 repeated doses of 500μM freshly prepared FTA loaded HNPs via IN or intravenous (IV) application. Pre-treatment and post-treatment tumor sizes were determined with MRI. After a treatment period of 5days, IN applied FTA loaded HNPs achieved a significant decrease of 55.7% in tumor area, equal to IV applied FTA loaded HNPs. Herewith, we showed the potential utility of IN application of FTA loaded HNPs as a non-invasive approach in glioblastoma treatment.
新型药物输送系统在研究和临床领域非常需要，通过将高浓度的抗肿瘤药物递送到靶位而不损伤健康组织，从而有效地治疗神经胶质瘤。鼻腔（IN）给药是一种非侵入性向大脑输送药物的替代途径，可绕过血脑屏障（BBB）并消除全身副作用。本研究评估了法呢基硫水杨酸（FTA）负载（脂质-阳离子）脂质-PEG-PLGA 杂化纳米颗粒（HNP）经 IN 给药后在大鼠中的抗肿瘤功效。制备、表征并评价了 FTA 负载的 HNP 的细胞毒性。将大鼠神经胶质瘤 2 （RG2）细胞单侧植入雌性 Wistar 大鼠右侧纹状体。10 天后，荷瘤大鼠接受未治疗或通过 IN 或静脉（IV）应用 500μM 新鲜制备的 FTA 负载 HNP 重复 5 次。用 MRI 确定治疗前和治疗后的肿瘤大小。经过 5 天的治疗期后，IN 应用的 FTA 负载 HNP 可使肿瘤面积显著减少 55.7%，与 IV 应用的 FTA 负载 HNP 相当。在此，我们展示了 IN 应用 FTA 负载 HNP 作为神经胶质瘤治疗的非侵入性方法的潜力。
