Construction of MIL-101 (Fe)/GO Composite Carrier and Suitability and Sustained-Release Characteristics for Co-Loading Luteolin and Matrine
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摘要:
目的 探讨铁基金属有机框架材料MIL-101(Fe)与氧化石墨烯(GO)复合载体[MIL-101(Fe)/GO]共载2种抗肿瘤有效成分木犀草素和苦参碱的适宜性及体外释放性能。 方法 采用溶剂热法制备MIL-101(Fe)与MIL-101(Fe)/GO复合载体, 采用扫描电子显微镜分析(SEM)、X射线衍射分析(XRD)、比表面积及孔径结构分析(BET)、红外光谱分析(FT-IR)等方法进行结构表征, 采用CCK-8细胞实验考察2种载体的安全性, 采用体外溶出试验, 以HPLC法测定木犀草素与苦参碱在MIL-101(Fe)/GO中的载药量与释放量。 结果 扫描电镜结果可见制得的MIL-101(Fe)/GO复合载体为多面体晶型结构复合体系; 细胞活力实验结果表明, 2种载体对小鼠成纤维细胞未产生抑制。木犀草素与苦参碱在MIL-101(Fe)中的载药量分别为14.1%、10.63%, 在MIL-101(Fe)/GO中载药量分别为20.74%、14.1%;体外释放实验结果表明, 在pH=5的条件下, MIL-101(Fe)/GO在72 h内可释放出23.92%的木犀草素与32.07%的苦参碱, 而在pH=7.4的条件下, MIL-101(Fe)/GO在相同时间内可释放出8.84%的木犀草素与36.19%的苦参碱。 结论 MIL-101(Fe)/GO复合载体的载药量更高, 作为pH响应型复合载体, 可有效实现对木犀草素的酸性pH响应释放及其与苦参碱的缓慢释放, 为实现多药递送持久释放的抗肿瘤药物设计提供新的思路。 Abstract:OBJECTIVE To investigate the suitability and in vitro release performance of two antitumor active ingredients luteolin and matrine co-loaded with the composite carrier of iron fund organic frame material MIL-101(Fe) and graphene oxide (GO). METHODS MIL-101 (Fe) and MIL-101(Fe)/GO composite carriers were prepared by the solvothermal method. The structures were characterized by SEM, XRD, BET and FT-IR. CCK-8 cell experiments were used to investigate the safety of the two carriers. The drug loading and release of luteolin and matrine in the composite carrier were determined by HPLC. RESULTS The results of scanning electron microscopy showed that the MIL-101(Fe)/GO composite carrier was a polyhedral crystal structure composite system. The results of cell viability test showed that the two vectors did not inhibit mouse fibroblasts. The loading capacity of luteolin and matrine in MIL-101(Fe) were 14.1% and 10.63%, respectively; and the loading capacities of these two drugs in MIL-101(Fe)/GO were 20.74% and 14.1%, respectively. The results of in vitro release experiment showed that under the condition of pH=5, the complex carrier could release 23.92% luteolin and 32.07% matrine within 72 h, while under the condition of pH=7.4, the complex carrier could release 8.84% luteolin and 36.19% matrine within the same time. CONCLUSIONS MIL-101(Fe)/GO composite carrier has higher drug loading capacity. As a pH-responsive composite carrier, it can effectively achieve the acidic pH response release of luteolin and slow release with matrine, providing a new idea for the design of anti-tumor drugs with multi-drug delivery and sustained release. -
Key words:
- MIL-101(Fe) /
- graphene oxide /
- luteolin /
- matrine /
- drug co-loading /
- in vitro release
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表 1 MIL-101(Fe)与MIL-101(Fe)/GO的比表面积与孔结构参数
Table 1. Specific surface area and pore structure parameters of MIL-101 (Fe) and MIL-101 (Fe)/GO
材料 BET比表面积/(m2·g-1) Langmuir表面积/(m2·g-1) 孔容/(cm3·g-1) 孔径/nm MIL-101(Fe) 487.485 527.306 0.344 2.819 MIL-101(Fe)/GO 292.930 307.173 0.268 3.657 表 2 2种材料载药量(%)
Table 2. The drug load of two material(%)
载体组别 木犀草素 苦参碱 MIL-101(Fe) 14.68 10.63 MIL-101(Fe)/GO 20.74 14.10 -
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