基于温控响应的壳聚糖原位凝胶配方，结合负载5-FU的纳米红细胞用于纤维肉瘤局部化疗
A thermoresponsive chitosan-based in situ gel formulation incorporated with 5-FU loaded nanoerythrosomes for fibrosarcoma local chemotherapy
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影响因子:8.5
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
DOI:
10.1016/j.ijbiomac.2024.134781
摘要
在肿瘤部位进行药物局部给药并延长药物作用时间显示出作为癌症治疗有潜力的前景。在本研究中，利用壳聚糖和聚氧丙烯酰胺407的温度诱导相变，构建了一种可注射水凝胶，封装负载5-FU的纳米红细胞（5-FU-NER-gel）。发现5-FU-NER为球形，直径约为115 ± 20 nm，表面电位为-7.06 ± 0.4。药物装载效率约为40%。当水凝胶暴露于体温或皮下注射时，15秒内即可形成原位凝胶。在pH 7.4和6.8条件下观察到持续释放特性，24小时内总释放的5-FU分别为76.57 ± 4.4%和98.07 ± 6.31%。MTT、活/死染色和迁移实验确认了载药载体的细胞相容性及其作为化疗药物制剂的有效性。在体内异体自体移植模型的抗肿瘤评估中，显示在14天内肿瘤生长抑制率达90%。因此，所获得的含有负载5-FU的纳米红细胞的可注射壳聚糖水凝胶展现出作为局部及增强药物传递候选的潜力。
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.