研究动态
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一种基于热响应壳聚糖的原位凝胶制剂,与负载 5-FU 的纳米红细胞体结合,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.

发表日期:2024 Aug 14
作者: Parisa Javadi, Mohammad Ali Derakhshan, Reza Heidari, Hajar Ashrafi, Negar Azarpira, Mohammad Ali Shahbazi, Amir Azadi
来源: Int J Biol Macromol

摘要:

长时间在肿瘤部位局部给药显示出作为一种有前途的癌症治疗方法的潜力。在本研究中,利用壳聚糖和泊洛沙姆 407 的温度诱导相变来构建封装 5-FU 负载的纳米红体的可注射水凝胶 (5-FU-NER-gel)。发现5-FU-NER是球形的,直径约为115±20nm,表面电势为-7.06±0.4。载药效率约为40%。当凝胶暴露于体温或皮下注射时,15秒内发生原位凝胶形成。在 pH7.4 和 6.8 下观察到缓释曲线,24 小时内 5-FU 总释放量分别为 76.57±4.4 和 98.07±6.31。 MTT、活/死和迁移测定证实了药物载体的细胞相容性及其作为化疗制剂的有效性。经过皮下自体移植模型体内抗肿瘤评估,14天内肿瘤生长抑制率为90%。因此,所获得的含有 5-FU 负载的纳米红细胞体的可注射壳聚糖基水凝胶显示出作为肿瘤部位局部和增强化疗药物递送的候选者的巨大潜力。版权所有 © 2024。由 Elsevier B.V. 出版。
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.Copyright © 2024. Published by Elsevier B.V.