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Co-encapsulation of superparamagnetic nanoparticles and doxorubicin in PLGA nanocarriers: Development, characterization and in vitro antitumor efficacy in glioma cells
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.9 ) Pub Date : 2019-10-16 , DOI: 10.1016/j.ejpb.2019.10.004
Edurne Luque-Michel , Víctor Sebastian , Ane Larrea , Clara Marquina , María J. Blanco-Prieto

With a very poor prognosis and no clear etiology, glioma is the most aggressive cancer in the brain. Thanks to its versatility, nanomedicine is a promising option to overcome the limitations on chemotherapy imposed by the blood brain barrier (BBB). The objective of this paper was to obtain monitored tumor-targeted therapeutic nanoparticles (NPs). To that end, theranostic surfactant-coated polymer poly-Lactic-co-Glycolic Acid (PLGA) nanoplatform encapsulating doxorubicin hydrochloride (DOX) and superparamagnetic iron oxide NPs (SPIONs) were developed. Different non-ionic surfactants known as BBB crossing enhancers (Tween 80, Brij-35, Pluronic F68 or Vitamin E-TPGS) were used to develop 4 types of theranostic nanoplatforms, which were characterized in terms of size and morphology by DLS, TEM and STEM-HAADF analyses. Moreover, the 3-month stability test, the therapeutic efficacy against different glioma cell lines (U87-MG, 9L/LacZ and patient derived-neuronal stem cells) and the Magnetic Resonance Imaging (MRI) relaxivity were studied. Results showed that the synthesised nanoplatforms were stable at 4 °C after their lyophilization, being that of paramount importance to ensure a long-term stability in a future in vivo application. Furthermore, the theranostic nanoplatforms were efficient in the in vitro treatment of glioma cells, proving to have imaging efficacy as MRI contrast agents. Our results show an efficient loading of drugs and good value of the relaxivity. Therefore, the efficient theranostic hybrid nanoplatform developed here could be used to perform MRI-guided delivery of hydrophobic drugs.



中文翻译:

PLGA纳米载体中超顺磁性纳米粒子和阿霉素的共包封:胶质瘤细胞的发展,表征和体外抗肿瘤功效。

神经胶质瘤的预后非常差,病因不明确,是大脑中最具有侵略性的癌症。由于其多功能性,纳米药物是克服血脑屏障(BBB)对化学疗法的局限性的有前途的选择。本文的目的是获得受监测的靶向肿瘤的治疗性纳米颗粒(NPs)。为此,开发了包封了阿霉素盐酸盐(DOX)和超顺磁性氧化铁NP(SPIONs)的涂有表面活性剂涂层的聚合物聚乳酸-乙醇酸共聚物(PLGA)纳米平台。使用了称为BBB交叉增强剂的不同非离子表面活性剂(吐温80,Brij-35,Pluronic F68或维生素E-TPGS)来开发4种类型的扩张剂纳米平台,并通过DLS,TEM和DLS对其尺寸和形态进行了表征。 STEM-HAADF分析。而且,在3个月的稳定性测试中,研究了针对不同神经胶质瘤细胞系(U87-MG,9L / LacZ和患者来源的神经元干细胞)的治疗效果以及磁共振成像(MRI)弛豫性。结果表明,所合成的纳米平台冻干后在4°C下稳定,这对于确保将来的长期稳定性至关重要。体内应用。此外,治疗性纳米平台在神经胶质瘤细胞的体外治疗中是有效的,证明其具有作为MRI造影剂的成像功效。我们的结果表明有效装载药物和良好的放松价值。因此,此处开发的有效的治疗药物杂合纳米平台可用于执行MRI引导的疏水性药物递送。

更新日期:2019-10-16
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