用于结直肠癌治疗的伊立替康负载磁铁矿-二氧化硅核-壳系统。
Irinotecan-loaded magnetite-silica core-shell systems for colorectal cancer treatment.
发表日期:2024 Jul 04
作者:
Cristina Chircov, Mihai-Cătălin Petcu, Bogdan Stefan Vasile, Bogdan Purcăreanu, Adrian Ionut Nicoară, Ovidiu Cristian Oprea, Roxana Cristina Popescu
来源:
INTERNATIONAL JOURNAL OF PHARMACEUTICS
摘要:
结直肠癌是一种世界范围内传播的癌症,与肺癌、乳腺癌和前列腺癌一起被视为主要死亡原因之一。由于传统的手术切除和化疗的效率有限,因此使用确保细胞抑制剂受控释放的替代药物输送系统具有巨大的治疗潜力。在这方面,本研究旨在开发和评估一系列负载伊立替康的磁铁矿-二氧化硅核-壳系统的效率。磁铁矿颗粒是通过溶剂热处理获得的,而二氧化硅壳是通过Stöber方法直接在磁铁矿颗粒表面获得的。随后,通过配备高环形角暗场探测器的 X 射线衍射(XRD)和(高分辨率)透射电子显微镜((HR-)TEM)对核-壳系统进行物理化学和形态结构评估( HAADF)用于元素映射。伊立替康负载后,通过傅里叶变换红外光谱(FT-IR)、热重分析和差示扫描量热法(TG-DSC)以及紫外-可见分光光度法对药物递送系统进行评估。此外,采用 Brunauer-Emmett-Teller (BET) 方法来确定系统的表面积和孔体积。通过对正常细胞和癌细胞进行 MTT 测定来研究核壳的生物学功能。研究结果证实了高度结晶的磁铁矿颗粒的形成,该颗粒包含核和尺寸在 2 至 7 nm 之间的介孔二氧化硅层作为壳。此外,药物负载和释放取决于二氧化硅合成程序的类型,因为缺乏十六烷基三甲基溴化铵(CTAB)导致药物负载较高但累积释放较低。此外,纳米结构系统表现出对 HT-29 结直肠腺癌细胞的靶向效率,与正常 L929 成纤维细胞一样,细胞活力高于原始药物。通过这种方式,本研究提供了开发适用于癌症治疗的药物输送系统的方法和程序。版权所有 © 2024。由 Elsevier B.V. 出版。
Colorectal cancer represents a worldwide spread type of cancer and it is regarded as one of the leading death causes, along with lung, breast, and prostate cancers. Since conventional surgical resection and chemotherapy proved limited efficiency, the use of alternative drug delivery systems that ensure the controlled release of cytostatic agents possess immense potential for treatment. In this regard, the present study aimed to develop and evaluate the efficiency of a series of irinotecan-loaded magnetite-silica core-shell systems. The magnetite particles were obtained through a solvothermal treatment, while the silica shell was obtained through the Stöber method directly onto the surface of magnetite particles. Subsequently, the core-shell systems were physico-chemically and morpho-structurally evaluated trough X-ray diffraction (XRD) and (high-resolution) transmission electron microscopy ((HR-)TEM) equipped with a High Annular Angular Dark Field Detector (HAADF) for elemental mapping. After the irinotecan loading, the drug delivery systems were evaluated through Fourier-transform infrared spectroscopy (FT-IR), thermogravimetry and differential scanning calorimetry (TG-DSC), and UV-Vis spectrophotometry. Additionally, the Brunauer-Emmett-Teller (BET) method was employed for determining the surface area and pore volume of the systems. The biological functionality of the core-shells was investigated through the MTT assay performed on both normal and cancer cells. The results of the study confirmed the formation of highly crystalline magnetite particles comprising the core and mesoporous silica layers of sizes varying between 2 and 7 nm as the shell. Additionally, the drug loading and release was dependent on the type of the silica synthesis procedure, since the lack of hexadecyltrimethylammonium bromide (CTAB) resulted in higher drug loading but lower cumulative release. Moreover, the nanostructured systems demonstrated a targeted efficiency towards HT-29 colorectal adenocarcinoma cells, as in the case of normal L929 fibroblast cells, the cell viability was higher than for the pristine drug. In this manner, this study provides the means and procedures for developing drug delivery systems with applicability in the treatment of cancer.Copyright © 2024. Published by Elsevier B.V.