关键词: Glycyrrhizin Methotrexate Mucositis Nanofiber Oral cancer

Mesh : Hyaluronic Acid / chemistry Nanofibers / chemistry Animals Methotrexate / administration & dosage chemistry pharmacology Mouth Neoplasms / drug therapy Humans Glycyrrhizic Acid / chemistry administration & dosage Cell Line, Tumor Drug Liberation Apoptosis / drug effects Drug Delivery Systems / methods Mice Male Drug Carriers / chemistry Anti-Inflammatory Agents / administration & dosage chemistry pharmacology

来  源:   DOI:10.1016/j.ijpharm.2024.124311

Abstract:
The challenges in treating oral cancer include the limited effectiveness and systemic side effects of conventional chemotherapy and radiation therapy. Hyaluronic acid (HA) based Glycyrrhizin (GL) and Methotrexate (MT) loaded localized delivery systems, specifically nanofiber (NF) based platforms, were developed to address these challenges. The electrospinning method was used for the successful fabrication of a homogenous NF membrane and characterized for morphology, drug entrapment efficiency, tensile strength, and ex-vivo mucoadhesive study. Also, it was evaluated for in-vitro drug release profile, ex-vivo drug permeability, in-vitro anti-inflammatory, apoptosis assay by MTT and flow, and against specific cell lines in order to determine their potential for therapeutic use. Superior tensile breaking force (50 g), mucoadhesive strength of 153 gm/cm2, drug permeability, and releasing properties of designed NF, making them perfect requirements for oral cavity delivery. The anticancer potential of MT in the MTT assay and flow cytometry analysis was significantly increased in oral epidermal carcinoma cell (KB cell) for drug-loaded NF with 63.97 ± 1.99 % apoptosis, at 24 h. With these incorporated, GL with MT in NF had an anti-inflammatory potential, also demonstrated in-vitro and in-vivo. In the Ehrlich Ascites Carcinoma (EAC) induced mice model, the optimal formulation\'s shows better potential for tumor regression when comparing the developed NF formulation to the drugs. Experimental results show that by lowering mucositis-related inflammation and enhancing the effectiveness of oral cancer treatment, a developed nanofiber-based local drug delivery system offers a feasible strategy for managing oral cancer.
摘要:
治疗口腔癌的挑战包括常规化学疗法和放射疗法的有限有效性和全身副作用。基于透明质酸(HA)的甘草酸(GL)和甲氨蝶呤(MT)加载的局部递送系统,特别是基于纳米纤维(NF)的平台,是为了应对这些挑战而开发的。静电纺丝方法用于成功制造均匀的NF膜,并表征其形态,药物包封效率,抗拉强度,和离体粘膜粘附研究。此外,对其进行了体外药物释放曲线评估,离体药物渗透性,体外抗炎,MTT法和流式细胞术检测细胞凋亡,并针对特定细胞系,以确定其治疗用途的潜力。优越的拉伸断裂力(50g),153gm/cm2的粘膜粘附强度,药物渗透性,以及设计的NF的释放特性,使他们对口腔分娩的完美要求。在MTT法和流式细胞术分析中MT的抗癌潜力在口腔表皮癌细胞(KB细胞)中对于载药NF具有63.97±1.99%的凋亡,在24小时。随着这些合并,具有NF中MT的GL具有抗炎潜力,也证明了在体外和体内。在艾氏腹水癌(EAC)诱导的小鼠模型中,当将开发的NF制剂与药物进行比较时,最佳制剂显示出更好的肿瘤消退潜力。实验结果表明,通过降低粘膜炎相关的炎症和增强口腔癌治疗的有效性,开发的基于纳米纤维的局部给药系统为治疗口腔癌提供了可行的策略.
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