纤维肉瘤局部化学疗法的5-FU纳米肌关节粒纳入了基于壳聚糖的原位凝胶配方
A thermoresponsive chitosan-based in situ gel formulation incorporated with 5-FU loaded nanoerythrosomes for fibrosarcoma local chemotherapy
影响因子:8.50000
分区:生物学2区 Top / 生化与分子生物学2区 应用化学2区 高分子科学2区
发表日期:2024 Oct
作者:
Parisa Javadi, Mohammad Ali Derakhshan, Reza Heidari, Hajar Ashrafi, Negar Azarpira, Mohammad Ali Shahbazi, Amir Azadi
摘要
在很长一段时间内，局部在肿瘤部位的药物给药显示了潜在的癌症治疗方法。在本研究中，壳聚糖和洛沙糖剂407的温度诱导的相过渡用于构建可注射的水凝胶，封装了5-FU的纳米持续体（5-FU-NER-GEL）。发现5-FU-NER是球形的，其直径约为115±20 nm，表面电位为-7.06±0.4。药物加载效率约为40％。当凝胶暴露于体温或皮下注射时，原位凝胶形成发生在15 s之内。在pH 7.4和6.8处观察到持续的释放曲线，总5-FU释放在24小时内分别为76.57±4.4和98.07±6.31。 MTT，Live/Dead和Migration Assays证实了药物携带者的细胞相容性及其作为化学治疗配方的有效性。在皮下自体移植模型中体内抗肿瘤评估后，证明14天内肿瘤生长抑制是90％。因此，获得的可注射的基于壳聚糖的水凝胶含有5-FU负载的纳米肌细胞说明了有希望的潜力，作为在肿瘤部位局部化疗和增强化学治疗剂的候选者的潜力。
Abstract
Local administration of drugs at tumor sites over an extended period of time shows potential as a promising approach for cancer treatment. In the present study, the temperature-induced phase transition of chitosan and poloxamer 407 is used to construct an injectable hydrogel encapsulating 5-FU-loaded nanoerythrosome (5-FU-NER-gel). The 5-FU-NERs were found to be spherical, measuring approximately 115 ± 20 nm in diameter and having a surface potential of -7.06 ± 0.4. The drug loading efficiency was approximately 40 %. In situ gel formation took place within 15 s when the gel was exposed to body temperature or subcutaneous injection. A sustained release profile was observed at pH 7.4 and 6.8, with a total 5-FU release of 76.57 ± 4.4 and 98.07 ± 6.31 in 24 h, respectively. MTT, Live/dead, and migration assays confirmed the cytocompatibility of the drug carrier and its effectiveness as a chemotherapeutic formulation. After in vivo antitumor assessment in a subcutaneous autograft model, it was demonstrated that tumor growth inhibition in 14 days was 90 %. Therefore, the obtained injectable chitosan-based hydrogel containing 5-FU-loaded nanoerythrosomes illustrated promising potential as a candidate for local and enhanced delivery of chemotherapeutics at the tumor site.