Kadhim Salma Hussein, Dehghan Gholamreza, Mahdavi Majid
Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Med Oncol. 2025 Feb 13;42(3):75. doi: 10.1007/s12032-025-02619-2.
As a fundamental approach to the treatment of acute myeloid leukemia (AML), chemotherapeutic agents face significant clinical challenges, including poor solubility and low bioavailability. In this context, solid lipid nanoparticles (SLNs) have emerged as a promising drug delivery system in oncologic therapies, owing to their advantageous characteristics, such as enhanced physical stability and controlled drug-release profiles. This study focuses on the synthesis of ciprofloxacin (CP)-loaded SLNs, aiming to enhance the anticancer efficacy of CP, an antibiotic recognized for its potential anticancer properties, while simultaneously reducing its associated side effects. Characterization of blank SLN and CP-SLN was conducted using dynamic light scattering (DLS), atomic force microscopy (AFM), UV-Vis spectrophotometry, and Fourier transform infrared spectroscopy (FTIR). In vitro release was carried out using dialysis bag method in isotonic phosphate buffer (pH = 7.4). The anticancer and pro-apoptotic effects of the CP-SLN formulation were assessed through cell viability assays, Hoechst staining, and Annexin V/PI flow cytometry. Additionally, expression levels of Bax, Bcl2, and p53 were analyzed via Real-Time PCR. The synthesized CP-SLN formulation exhibited optimal characteristics, including a particle size of 340-360 nm, a polydispersity index (PDI) of 0.4, and an entrapment efficiency of 90%. The in vitro drug release showed an initial burst release in the time points 4-10 h. Both CP and the CP-SLN formulations demonstrated significant anti-proliferative and pro-apoptotic effects on KG1-a cells, as indicated by the upregulation of the Bax/Bcl2 ratio and p53, resulting in G0/G1 cell cycle arrest and apoptosis induction. The results suggest that encapsulating CP in SLN enhances its anticancer and pro-apoptotic effects in KG1-a stem-like leukemia cells. Thus, CP-SLN may serve as a promising formulation for leukemia treatment and could improve the efficacy of other therapeutic agents.
作为治疗急性髓系白血病(AML)的基本方法,化疗药物面临着重大的临床挑战,包括溶解度差和生物利用度低。在这种情况下,固体脂质纳米粒(SLNs)作为一种有前景的药物递送系统出现在肿瘤治疗中,这得益于其诸如增强的物理稳定性和可控的药物释放曲线等优势特性。本研究聚焦于载环丙沙星(CP)的固体脂质纳米粒的合成,旨在增强CP的抗癌疗效,CP是一种因其潜在抗癌特性而被认可的抗生素,同时减少其相关副作用。使用动态光散射(DLS)、原子力显微镜(AFM)、紫外可见分光光度法和傅里叶变换红外光谱(FTIR)对空白固体脂质纳米粒和载环丙沙星固体脂质纳米粒进行表征。体外释放采用透析袋法在等渗磷酸盐缓冲液(pH = 7.4)中进行。通过细胞活力测定、Hoechst染色和膜联蛋白V/碘化丙啶流式细胞术评估载环丙沙星固体脂质纳米粒制剂的抗癌和促凋亡作用。此外,通过实时聚合酶链反应分析Bax、Bcl2和p53的表达水平。合成的载环丙沙星固体脂质纳米粒制剂表现出最佳特性,包括粒径为340 - 360 nm、多分散指数(PDI)为0.4以及包封率为90%。体外药物释放在4 - 10小时的时间点显示出初始突释。CP和载环丙沙星固体脂质纳米粒制剂均对KG1 - a细胞表现出显著的抗增殖和促凋亡作用,Bax/Bcl2比值和p53上调表明了这一点,导致G0/G1细胞周期停滞和凋亡诱导。结果表明,将CP包裹在固体脂质纳米粒中可增强其在KG1 - a白血病干细胞样细胞中的抗癌和促凋亡作用。因此,载环丙沙星固体脂质纳米粒可能是一种有前景的白血病治疗制剂,并且可以提高其他治疗药物的疗效。