超临界CO<sub>2</sub>流体辅助中性γ-CD-MOF载小白菊内酯工艺优化与体外释放评价

郭静雯; 何远志; 张永太; 冯年平

doi:10.14148/j.issn.1672-0482.2022.0615

超临界CO₂流体辅助中性γ-CD-MOF载小白菊内酯工艺优化与体外释放评价

doi: 10.14148/j.issn.1672-0482.2022.0615

上海中医药大学中药学院, 上海 201203

基金项目:

国家自然科学基金面上项目 82074279

上海市东方学者特聘教授资助资金 TP2020054

国家中医药管理局中药特色技术传承人才培训项目 T20194828003

详细信息

作者简介:
郭静雯, 女, 硕士研究生, E-mail: guojingwen1997@163.com

通讯作者:
冯年平, 男, 教授, 主要从事中药新型给药系统研究, E-mail: npfeng@shutcm.edu.cn

中图分类号: R273
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- 文章访问数: 183
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- 被引次数: 0
出版历程
- 收稿日期: 2022-03-21
- 网络出版日期: 2022-07-09
- 发布日期: 2022-07-10

Optimization and in vitro Release Evaluation of Parthenolide-Loaded Neutral γ-CD-MOF Assisted with ScCO₂ Fluid

Department of Pharmaceutical Sciences, Shanghai University of Chinese Medicine, Shanghai 201203, China

摘要

摘要: 目的以K⁺离子与γ-环糊精(γ-CD)自组装形成的环糊精金属有机骨架(γ-CD-MOF)作为小白菊内酯(Parthenolide, PTL)的载体, 以期改善PTL的溶解性和稳定性。方法采用溶剂热法制备γ-CD-MOF, 中性化处理得Neu-γ-CD-MOF, 再以超临界CO₂流体技术(Supercritical carbon dioxide fluid, scCO₂)活化Neu-γ-CD-MOF。考察并优化了scCO₂法载药工艺, 对载PTL的Neu-γ-CD-MOF(PTL@Neu-γ-CD-MOF)进行系统表征和体外释药评价。结果 scCO₂活化后可得分散均一的Neu-γ-CD-MOF。使用scCO₂辅助PTL载入Neu-γ-CD-MOF, 载药量可高达26.58%。以优化工艺制备的PTL@Neu-γ-CD-MOF可显著增加PTL的水溶解度, 药物在水中的表观溶解度为PTL原料药的2.2倍, 并显著提高药物溶出速率及累积释放度。结论 scCO₂法可提高Neu-γ-CD-MOF的载药效率, PTL@Neu-γ-CD-MOF纳米粒可解决PTL低溶解度的问题, 改善药物溶出特征, 从而实现PTL的高效递送。
- γ-环糊精金属有机骨架 /
- 小白菊内酯 /
- 超临界二氧化碳流体 /
- 纳米递药系统
Abstract: OBJECTIVES Cyclodextrin metal-organic framework (γ-CD-MOF) formed self-assembly by K⁺ions and γ-cyclodextrin (γ-CD) was used as the carrier of PTL in order to improve its solubility and stability. METHODS γ-CD-MOF was prepared by solvothermal method. Neu-γ-CD-MOF was obtained by neutralization and then activated by supercritical carbon dioxide fluid (scCO₂). The preparation of PTL-loaded Neu-γ-CD-MOF assisted with scCO₂ method was optimized, and the PTL@Neu-γ-CD-MOF was systematically characterized and evaluated for release in vitro. RESULTS Neu-γ-CD-MOF with nanoscale particle size and uniform dispersion is obtained after scCO₂ activation. Drug loading of PTL@Neu-γ-CD-MOF is 26.58% assisted with scCO₂. PTL@Neu-γ-CD-MOF significantly increases the water solubility of PTL, and the apparent solubility of PTL in water is 2.2 times of free PTL. The dissolution rate and cumulative release of PTL are both significantly improved. CONCLUSION ScCO₂ can improve drug loading efficiency of Neu-γ-CD-MOF, and PTL@Neu-γ-CD-MOF increases the solubility and dissolution rate of PTL effectively.
- γ-cyclodextrin metal-organic framework /
- parthenolide /
- supercritical carbon dioxide fluid /
- nano drug delivery system

HTML全文

图 1 扫描电镜图

注：A.二氯甲烷激活Neu-γ-CD-MOF; B.scCO₂激活Neu-γ-CD-MOF

Figure 1. SEM images

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图 2 Neu-γ-CD-MOF激活前/后和scCO₂载药后XRD衍射图谱

Figure 2. XRD of PTL, Neu-γ-CD-MOF, scCO₂ actived Neu-γ-CD-MOF, and PTL@Neu-γ-CD-MOF

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图 3 Neu-γ-CD-MOF、PTL以及PTL@Neu-γ-CD-MOF的FT-IR光谱

Figure 3. FT-IR spectra of Neu-γ-CD-MOF, PTL, and PTL@Neu-γ-CD-MOF

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图 4 PTL@Neu-γ-CD-MOF、PTL@γ-CD、PTL在PBS中的溶出曲线(x±s, n=3)

Figure 4. In vitro dissolution curves of PTL@Neu-γ-CD-MOF, PTL@γ-CD, and PTL in PBS (x±s, n=3)

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表 1 不同干燥方式制备γ-CD-MOF的粒径

Table 1. Mean size of γ-CD-MOF prepared by different drying methods

MOF	粒径/nm	PDI
二氯甲烷激活γ-CD-MOF scCO₂激活γ-CD-MOF 二氯甲烷激活Neu-γ-CD-MOF scCO₂激活Neu-γ-CD-MOF	275.8 117.3 510.6 138.7	0.375 0.174 0.273 0.075

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表 2 载药浓度考察(x±s, n=3)

Table 2. Drug loading of Neu-γ-CD-MOF processed with different PTL concentration (x±s, n=3)

载药浓度/(g·L^-1)	载药量/%
30	13.53±0.38
50	15.35±0.22
60	15.60±0.37

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表 3 不同干燥方式制备Neu-γ-CD-MOF的载药量(x±s, n=3)

Table 3. Drug loading of Neu-γ-CD-MOF processed with different drying methods (x±s, n=3)

Neu-γ-CD-MOF 干燥方式	载药量/%
Neu-γ-CD-MOF 干燥方式	常规载药	scCO₂载药
γ-CD	11.87±0.21	—
溶剂热法(二氯甲烷活化)	15.35±0.22	16.02±0.42
scCO₂干燥(二氯甲烷活化)	16.06±0.22	26.58±0.43

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表 4 PTL原料药、PTL@γ-CD及PTL@Neu-γ-CD-MOF在水中的平衡溶解度(x±s, n=3)

Table 4. Solubility of PTL, PTL@γ-CD, and PTL@CD-MOF in water (x±s, n=3)

样品	平衡溶解度/(μg·mL^-1)
PTL原料药	549.02±0.69
PTL@γ-CD	822.23±0.31
PTL@Neu-γ-CD-MOF	1 193.94±1.02

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