A potential non-invasive glioblastoma treatment: Nose-to-brain delivery of farnesylthiosalicylic acid incorporated hybrid nanoparticles

被引:42
|
作者
Sekerdag, Emine [1 ,2 ]
Lule, Sevda [3 ,4 ,5 ,6 ]
Pehlivan, Sibel Bozdag [1 ]
Ozturk, Naile [1 ]
Kara, Asli [7 ,8 ]
Kaffashi, Abbas [7 ]
Vural, Imran [1 ]
Isikay, Ilkay [9 ]
Yavuz, Burcin [1 ]
Oguzh, Kader Karli [10 ]
Soylemezoglu, Figen [11 ]
Gursoy-Ozdemir, Yasemin [2 ,12 ]
Mut, Melike
机构
[1] Hacettepe Univ, Fac Pharm, Dept Pharmaceut Technol, Ankara, Turkey
[2] Koc Univ, Res Ctr Translat Med, Neurosci Res Lab, Istanbul, Turkey
[3] Hacettepe Univ, Inst Neurol Sci & Psychiat, Ankara, Turkey
[4] Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA
[5] Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA USA
[6] Harvard Med Sch, Charlestown, MA USA
[7] Hacettepe Univ, Fac Pharm, Dept Nanotechnol & Nanomed, Ankara, Turkey
[8] Hitit Univ, Fac Art & Sci, Dept Biol, Corum, Turkey
[9] Hacettepe Univ, Fac Med, Dept Neurosurg, Ankara, Turkey
[10] Hacettepe Univ, Fac Med, Dept Radiol, Ankara, Turkey
[11] Hacettepe Univ, Fac Med, Dept Pathol, Ankara, Turkey
[12] Koc Univ, Sch Med, Dept Neurol, Istanbul, Turkey
关键词
Hybrid nanoparticles; Glioblastoma; Drug delivery; Nose-to-brain; Farnesylthiosalicylic acid; FARNESYL THIOSALICYLIC ACID; RAS INHIBITOR; TUMOR-GROWTH; TARGETED DELIVERY; DRUG-DELIVERY; SALIRASIB; SUPPRESSION; TRANSPORT; THERAPY; SYSTEMS;
D O I
10.1016/j.jconrel.2017.06.032
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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-brainbarrier (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. 10 days later, glioma bearing rats received either no treatment, or 5 repeated doses of 500 mu M 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 5 days, 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.
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页码:187 / 198
页数:12
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