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首页> 外文期刊>Journal of biomedical materials research. Part B, Applied biomaterials. >Effects of solvent used for fabrication on drug loading and release kinetics of electrosprayed temozolomide-loaded PLGA microparticles for the treatment of glioblastoma
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Effects of solvent used for fabrication on drug loading and release kinetics of electrosprayed temozolomide-loaded PLGA microparticles for the treatment of glioblastoma

机译：溶剂用于制造对电喷雾泛唑粒素的PLGA微粒的药物载荷和释放动力学治疗胶质母细胞瘤的释放动力学

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摘要

Glioblastoma multiforme (GBM) is the most common and invasive form of malignant brain tumors and despite advances in surgery, radiotherapy, and chemotherapy, the survival of patients with GBM still remains poor. Temozolomide (TMZ) is the chemotherapy drug that is most commonly given orally after surgical resection of these tumors. In this study, the effects of solvents (i.e., dichloromethane and acetonitrile) used for the fabrication of electrosprayed TMZ-loaded poly(lactic-co-glycolic acid) (PLGA) on drug loading, loading efficiency, drug release kinetics, surface morphology, and particle size were investigated. The results from this study demonstrated that by using a larger volume of a solvent with higher polarity (i.e., acetonitrile) which allows for a higher amount of hydrophilic TMZ to dissolve into the polymer solution, higher drug loading could be achieved. However, the particles fabricated with high amount of acetonitrile, which has a lower vapor pressure, had large pores and a smaller diameter which led to an initial burst release and high cumulative release at the end of the study. An optimal combination of the two solvents is needed to result in particles with a good amount of loading and minimal initial burst release. The electrosprayed microparticles were able to illicit a cytotoxic response in U-87 MG glioblastoma cells at a lower concentration of drug compared to the free drug. This work indicated that electrospraying is a promising method for the fabrication of TMZ-loaded PLGA microparticles for the treatment of GBM and solvent composition can be altered to control drug loading and release kinetics. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2317-2324, 2019.
机译：胶质母细胞瘤多形体（GBM）是最常见和侵入性的恶性脑肿瘤形式，尽管手术，放疗和化疗进展，GBM患者的存活率仍然差。 Temozolomide（TMZ）是在手术切除这些肿瘤后口服最常给出的化疗药物。在该研究中，溶剂（即二氯甲烷和乙腈）的影响用于制造电喷雾的TMZ负载的聚（乳酸 - 共乙醇酸）（PLGA）对药物负载，装载效率，药物释放动力学，表面形态，并研究了粒度。本研究的结果证明，通过使用允许较高的极性（即乙腈）的较大体积的溶剂，其允许较高量的亲水性TMZ溶解到聚合物溶液中，可以实现更高的药物负载。然而，具有较高蒸气压的乙腈制造的颗粒具有大的孔隙和较小的直径，其导致初始爆发释放和在研究结束时的累积释放。需要两种溶剂的最佳组合来导致具有良好量的载荷和最小初始爆发释放的颗粒。与游离药物相比，电喷雾的微粒能够以较低的药物浓度为U-87mg胶质母细胞瘤细胞毒性反应。这项工作表明，电喷雾是用于制备TMZ负载的PLGA微粒的有希望的方法，用于治疗GBM，可以改变溶剂组合物以控制药物载荷和释放动力学。 （c）2019 Wiley期刊，Inc.J生物保解员A件B：苹果生物机107B：2317-2324,2019。

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