Department of Pharmaceutics, ISF College of Pharmacy, Moga, Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab, 142001, India.
Department of Pharmacology, ISF College of Pharmacy, Moga, Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab, 142001, India.
Drug Deliv Transl Res. 2024 Dec;14(12):3422-3437. doi: 10.1007/s13346-024-01546-5. Epub 2024 Apr 4.
Chemotherapy-induced cognitive impairment (CICI), also known as "chemobrain," is a common side effect of breast cancer therapy which causes oxidative stress and generation of reactive oxygen species (ROS). Ferulic acid (FA), a natural polyphenol, belongs to BCS class II is confirmed to have nootropic, neuroprotective and antioxidant effects. Here, we have developed FA solid dispersion (SD) in order to enhance its therapeutic potential against chemobrain. An amorphous ferulic acid loaded leucin solid dispersion (FA-Leu SD) was prepared by utilizing amino acid through spray-drying technique. The solid-state characterization was carried out via Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM). Additionally, in-vitro release studies and antioxidant assay were also performed along with in-vivo locomotor, biochemical and histopathological analysis. The physical properties showed that FA-Leu SD so formed exhibited spherical, irregular surface hollow cavity of along with broad melting endotherm as observed from FE-SEM and DSC results. The XRD spectra demonstrated absence of sharp and intense peaks in FA-Leu SD which evidenced for complete encapsulation of drug into carrier. Moreover, in-vitro drug release studies over a period of 5 h in PBS (pH 7.4) displayed a significant enhanced release in the first hr (68. 49 ± 5.39%) and in-vitro DPPH assay displayed greater antioxidant potential of FA in FA-Leu SD. Furthermore, the in-vivo behavioral findings of FA-Leu SD (equivalent to 150 mg/kg of free FA) exhibited positive results accompanied by in-vivo biochemical and molecular TNF-α showed a significant difference (p < 0.001) vis-à-vis DOX treated group upon DOX + FA-Leu SD. Additionally, histopathological analysis revealed neuroprotective effects of FA-Leu SD together with declined oxidative stress due to antioxidant potential of FA which was induced by anticancer drug doxorubicin (DOX). Overall, the above findings concluded that spray-dried FA-Leu SD could be useful for the treatment of chemotherapy induced cognitive impairment.
化疗诱导的认知障碍（CICI），也称为“化疗脑”，是乳腺癌治疗的常见副作用，会导致氧化应激和活性氧（ROS）的产生。阿魏酸（FA）是一种天然多酚，属于 BCS 类 II，已被证实具有益智、神经保护和抗氧化作用。在这里，我们开发了 FA 固体分散体（SD），以增强其治疗化疗脑的潜力。通过喷雾干燥技术，利用氨基酸制备了载有亮氨酸的阿魏酸负载固体分散体（FA-Leu SD）。通过傅里叶变换红外光谱（FT-IR）、差示扫描量热法（DSC）、X 射线衍射（XRD）和场发射扫描电子显微镜（FE-SEM）对固体状态进行了表征。此外，还进行了体外释放研究和抗氧化测定以及体内运动、生化和组织病理学分析。物理性质表明，形成的 FA-Leu SD 表现出球形、不规则表面的空心腔以及从 FE-SEM 和 DSC 结果观察到的宽熔融吸热峰。XRD 图谱表明，FA-Leu SD 中没有尖锐和强烈的峰，这证明药物完全被包裹在载体中。此外，在 PBS（pH 7.4）中进行的 5 小时体外药物释放研究显示，在第一小时内（68.49±5.39%）显著增强了药物释放，体外 DPPH 测定显示 FA-Leu SD 中 FA 的抗氧化潜力更大。此外，FA-Leu SD 的体内行为研究结果（相当于 150mg/kg 的游离 FA）显示出积极的结果，同时体内生化和分子 TNF-α与 DOX 处理组相比显示出显著差异（p<0.001）。此外，组织病理学分析显示，FA-Leu SD 具有神经保护作用，同时由于抗癌药物阿霉素（DOX）诱导的 FA 的抗氧化潜力降低了氧化应激。总的来说，上述研究结果表明，喷雾干燥的 FA-Leu SD 可用于治疗化疗引起的认知障碍。
