Preparation of apigenin nanoparticles by combining subcritical water technology with freeze-drying processing

doi:10.11949/0438-1157.20200049

Abstract

Abstract:

Under the system of solvent(subcritical water)-antisolvent(deionized water), based on the combination of subcritical water technology and freeze-drying processing, we prepared apigenin nanoparticles by nanocrystallization and modification. The study comprehensively explores the influencing factors, including the temperature of desolvation, the temperature of subcritical water, the pressure of reaction system, and surfactant concentration in the process of the granulation. The study compares raw materials and products through scanning electronic microscopy (SEM), Fourier transform infrared spectrophotometry (FTIR), X-ray diffraction (XRD) and mass spectrometry (MS). The results show that when the antisolvent temperature is 0℃, the subcritical water temperature is 160℃, the reaction pressure is 5 MPa, and the surfactant γ-cyclodextrin mass fraction is 5%, the particle size can be obtained at range 20—30 nm, the nanoparticles are evenly distributed, with high stability and low crystallinity. The preparation method of apigenin nanoparticles reported in this article, without the participation of organic solvents in the whole process, is easy for biomedical promotion, and provides a reference for the design and development of oral drugs based on apigenin.

Key words: apigenin, subcritical water, antisolvent, granulation, green synthesis, nanoparticles

摘要：

在溶剂(亚临界水)-反溶剂(去离子水)体系下，利用溶剂反溶剂沉淀耦合冷冻干燥法，对芹菜素原料药进行了纳米化及改性，制备出了超细芹菜素颗粒及其水相分散体。系统地探究了反溶剂温度、亚临界水温度、反应压力、表面活性剂种类与浓度对造粒过程产生的影响，并通过扫描电子显微镜(SEM)、红外吸收光谱(FTIR)、X射线衍射 (XRD)、质谱分析(MS)等手段对原料药和产物进行了对比分析。结果表明，当反溶剂温度为0℃，亚临界水温度为160℃、反应压力为5 MPa、表面活性剂γ-环糊精的质量分数为5%时，可得到粒径在20~30 nm范围内，分布均匀，稳定程度较高且具有较低结晶度的纳米颗粒。本文报道的芹菜素纳米颗粒制备方法，全程无有机溶剂参与，易于生物医用推广，为基于芹菜素的口服药物设计与开发提供了参考。

关键词: 芹菜素, 亚临界水, 反溶剂, 造粒, 绿色制备, 纳米颗粒

CLC Number:

TQ 460.6⁺2

Jiyang TIAN, Yuanzuo ZOU, Yuan PU, Dan WANG. Preparation of apigenin nanoparticles by combining subcritical water technology with freeze-drying processing[J]. CIESC Journal, 2020, 71(6): 2768-2779.

田济阳, 邹源佐, 蒲源, 王丹. 亚临界水耦合冷冻干燥法制备芹菜素纳米分散体[J]. 化工学报, 2020, 71(6): 2768-2779.

Figures/Tables 15

Fig.1 Chemical structure of apigenin and SEM image of the raw material

Fig.2 Schematic diagram of apigenin nanoparticles preparation by using SBCW method

Fig.3 Schematic diagram of apigenin nanoparticles by using SBCW as solvent and deionized water as anti-solvent

Fig.4 SEM images of apigenin particles prepared at different anti-solvent temperature

Fig.5 SEM images of apigenin particles obtained from different volume ratio of solvent/anti-solvent

Fig.6 SEM images of apigenin particles obtained from different temperatures of SBCW

Fig.7 SEM images of apigenin particles obtained from different pressure

Fig.8 SEM images of apigenin particles prepared by using different surfactant

Fig.9 Chemical structure of γ-cyclooctapentylose

Fig.10 SEM images of apigenin particles prepared at different concentrations of γ-cyclooctapentylose

Fig.11 Effects of γ-cyclooctapentylose on stability of nanoparticles

Fig.12 FTIR spectra of the raw materials and apigenin nanoparticlesa—raw; b—apigenin nanoparticles; c—apigenin nanoparticles with γ-cyclooctapentylose

Fig.13 XRD patterns of raw materials and apigenin nanoparticlesa—raw; b—apigenin nanoparticles; c—apigenin nanoparticles with γ-cyclooctapentylose

Fig.14 UV-Vis spectra of raw materials and apigenin nanoparticlesa—raw; b—apigenin nanoparticles; c—apigenin nanoparticles with γ-cyclooctapentylose

Fig.15 Mass spectra of raw and apigenin nanoparticlesa—raw; b—apigenin nanoparticles; c—apigenin nanoparticles with γ-cyclooctapentylose

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