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层状双氢氧化物-泊洛沙姆 188 纳米复合材料基于剥离再组装,以提高甲氨蝶呤的细胞摄取和控制释放。

Layered double hydroxides - poloxamer 188 nanocomposites based on exfoliation reassembling for improved cellular uptake and controlled delivery of methotrexate.

机构信息

Analytical and Testing Center, Jiujiang University, Jiujiang, China.

School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang, China.

出版信息

Pharm Dev Technol. 2023 Oct;28(8):743-754. doi: 10.1080/10837450.2023.2246555. Epub 2023 Aug 16.

Abstract

Exploitation of advanced methotrexate (MTX) delivery with nanocomposites has important clinical application value. Poloxamer 188 micelle and layered double hydroxide loaded with MTX (LDH-MTX) by exfoliation reassembling were used to prepare LDH-MTX-poloxamer 188 nanocomposites with good dispersibility and efficient cellular uptake for controlled drug delivery. The LDH-MTX-poloxamer 188 nanocomposites with sphere-like morphology, of which the average hydrodynamic diameter was <100 nm, were shown to have better dispersion state than naked LDH-MTX. Importantly, the LDH-MTX-poloxamer 188 nanocomposites could achieve significant sustained drug release and have obvious pH dependent responsive release ability. In addition, these nanocomposites also exhibited long-term and excellent antitumor efficacy as opposed to pure MTX or LDH-MTX as evident from cell viability. More interestingly, compared to pure FITC used to simulate MTX, LDH nanocomposites labeled with FITC were considered to have better cell adhesion through cell uptake. Therefore, the studied nanocomposites of LDH-MTX-poloxamer 188 can be further used as a new advanced MTX delivery nanovehicles with desired properties in future therapeutic aspects.

摘要

利用纳米复合材料来开发先进的甲氨蝶呤(MTX)给药具有重要的临床应用价值。通过剥离再组装,将泊洛沙姆 188 胶束和负载 MTX 的层状双氢氧化物(LDH-MTX)用于制备具有良好分散性和高效细胞摄取能力的 LDH-MTX-泊洛沙姆 188 纳米复合材料,用于控制药物释放。具有类球形形态的 LDH-MTX-泊洛沙姆 188 纳米复合材料,其平均水动力直径<100nm,显示出比裸 LDH-MTX 更好的分散状态。重要的是,LDH-MTX-泊洛沙姆 188 纳米复合材料能够实现显著的持续药物释放,并具有明显的 pH 依赖性响应释放能力。此外,这些纳米复合材料还表现出长期和优异的抗肿瘤疗效,与纯 MTX 或 LDH-MTX 相比,细胞活力明显。更有趣的是,与用于模拟 MTX 的纯 FITC 相比,用 FITC 标记的 LDH 纳米复合材料被认为通过细胞摄取具有更好的细胞粘附性。因此,研究中的 LDH-MTX-泊洛沙姆 188 纳米复合材料可以进一步用作具有所需特性的新型先进 MTX 给药纳米载体,用于未来的治疗方面。

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