NH2-MCM-41的改性及其pH响应性释药的研究

doi:10.11949/0438-1157.20191604

摘要/Abstract

摘要：

采用正硅酸乙酯（TEOS）和3-氨丙基三乙氧基硅烷（APTES）通过共缩聚法合成介孔二氧化硅（MCM-41）。首先对其氨基修饰，再通过有机合成接枝—R基团（—R：—CHO、—OH、—CH₃、—COOH），制备得到Me-Ph-NH-MCM-41、OHC-Ph-NH-MCM-41、HO-Ph-NH-MCM-41、HOOC-Ph-NH-MCM-41四种不同的药物载体。利用FT-IR、Zeta电位、XRD和SEM对其结构和形貌表征，结果表明NH₂-MCM-41改性成功。以罗丹明B（RhB）为模型进行载药性能测试，并考察了此释药系统在模拟不同pH的体液下的敏感释药行为，同时探究了不同—R基团对释药的影响。结果显示，四种载体在中性条件下几乎不发生药物释放，通过改变环境体系pH可以有效控制药物释放，其释药行为可以用Korsmeyer-Peppas动力学模型来描述。实验表明，释药量：RhB@HOOC-Ph-NH-MCM-41>RhB@OHC-Ph-NH-MCM-41>RhB@HO-Ph-NH-MCM-41>RhB@Me-Ph-NH-MCM-41，不同—R基团的药物载体的pH响应性不同，其中RhB@HOOC-Ph-NH-MCM-41释药量在pH=1.2时可达57.87%，在用于药物智能控释材料方面具有一定的应用潜力。

关键词: 二氧化硅, 合成, 控制, 载体, 动力学模型

Abstract:

Mesoporous silica (MCM-41) was synthesized by copolycondensation of tetraethoxysilane (TEOS) and 3-aminopropyltriethoxysilane (APTES). Firstly, it was modified with amino group. Then, four different drug carriers, Me-Ph-NH-MCM-41, OHC-Ph-NH-MCM-41, HO-Ph-NH-MCM-41, and HOOC-Ph-NH-MCM-41, were synthesized by grafting —R group (—R: —CHO, —OH, —CH₃, —COOH), respectively. FT-IR, SEM, Zeta potential, and XRD were used to characterize its structure and morphology, indicating the successful synthesis of modified MCM-41. Rhodamine B (RhB) was used as a model for drug loading performance testing and the sensitive drug release behavior of this drug release system under different pH simulated humors was investigated. The effects of different —R groups on drug release were also explored. The results show that the four carriers hardly release drugs under neutral conditions. The drug release can be effectively controlled by changing the pH of the environmental system. The drug release behavior can be described by the Korsmeyer-Peppas kinetic model. The experiment showed that the drug release amount: RhB@HOOC-Ph-NH-MCM-41>RhB@OHC-Ph-NH-MCM-41>RhB@HO-Ph-NH-MCM-41>RhB@Me-Ph-NH-MCM-41. The pH-response of drug carriers with different —R groups was different, and the drug release amount of RhB@HOOC-Ph-NH-MCM-41 reached 57.87% at pH = 1.2, which has some potential applications in intelligent controlled release materials of drugs.

Key words: silica, synthesis, control, support, kinetic model

中图分类号:

O 643.36

徐彦芹, 秦钊, 王烨, 曹渊, 陈昌国, 王丹. NH₂-MCM-41的改性及其pH响应性释药的研究[J]. 化工学报, 2020, 71(10): 4783-4791.

Yanqin XU, Zhao QIN, Ye WANG, Yuan CAO, Changguo CHEN, Dan WANG. Study on modification of NH₂-MCM-41 and its pH-responsive drug release[J]. CIESC Journal, 2020, 71(10): 4783-4791.

图/表 11

图1 药物释放示意图

Fig.1 The schematic diagram of drug release

图2 NH2-MCM-41和四种药物载体的XRD谱图

Fig.2 XRD patterns of NH2-MCM-41 and four drug carriers

图3 NH2-MCM-41和四种药物载体的氮气吸附-脱附等温线和孔径分布图

Fig.3 N2 adsorption/desorption isotherm and pore size distribution of NH2-MCM-41 and four drug carriers

表1 NH2-MCM-41和四种药物载体的孔结构参数

Table 1 The pore structural parameter of NH2-MCM-41 and four drug carriers

载体	比表面积/ (m²/g)	孔容/(cm³/g)	孔径/nm
NH₂-MCM-41	937	0.801	3.98
Me-Ph-NH-MCM-41	368	0.323	3.03
OHC-Ph-NH-MCM-41	382	0.312	3.28
HO-Ph-NH-MCM-41	416	0.337	3.35
HOOC-Ph-NH-MCM-41	394	0.279	3.18

图4 NH2-MCM-41和四种药物载体的FT-IR谱图a—NH2-MCM-41; b—Me-Ph-NH-MCM-41; c—OHC-Ph-NH-MCM-41; d—HO-Ph-NH-MCM-41; e—HOOC-Ph-NH-MCM-41

Fig.4 FT-IR spectra of NH2-MCM-41 and four drug carriers

图5 四种药物载体电镜图

Fig.5 SEM images of four drug carriers

表2 NH2-MCM-41和四种药物载体的Zeta电位值

Table 2 Zeta potential of NH2-MCM-41 and four drug carriers

载体	Zeta电位值/mV
NH₂-MCM-41	+29.2
Me-Ph-NH-MCM-41	+8.1
OHC-Ph-NH-MCM-41	+4.2
HO-Ph-NH-MCM-41	-15.7
HOOC-Ph-NH-MCM-41	-31.4

表3 NH2-MCM-41和四种载药载体的吸附量及载药量

Table 3 The adsorption capacity and drug loading capacity of four drug carriers and NH2-MCM-41

载药载体	吸附量/(mg/g)	载药量/(mg/g)
RhB@NH₂-MCM-41	16.88	16.60
RhB@Me-Ph-NH-MCM-41	13.11	12.94
RhB@OHC-Ph-NH-MCM-41	13.45	13.27
RhB@HO-Ph-NH-MCM-41	13.11	12.94
RhB@HOOC-Ph-NH-MCM-41	12.83	12.65

表4 四种载药载体累积释药百分比

Table 4 Cumulative drug release percent of four drug carriers

载药载体

累积释药百分比/%

RhB@Me-Ph-NH-MCM-41

1.2

4.0

7.4

34.63

29.46

3.21

RhB@OHC-Ph-NH-MCM-41

1.2

4.0

7.4

52.03

42.63

3.12

RhB@HO-Ph-NH-MCM-41

1.2

4.0

7.4

43.94

35.45

3.06

RhB@HOOC-Ph-NH-MCM-41

1.2

4.0

7.4

57.87

47.54

3.09

表5 四种药物载体药物释放曲线拟合结果

Table 5 Results of drug release curve fitting of four drug carriers

载药载体	拟合方程	pH	相关系数R²
RhB@Me-Ph-NH-MCM-41	$M t M ∞ = 0.12461 t 0.26126 0.09507 t 0.29661 0.00050710 t 0.43314$	1.2	0.97413
		4.0	0.94715
		7.4	0.96264
RhB@OHC-Ph-NH-MCM-41	$M t M ∞ = 0.01585 t 0.307 0.12541 t 0.32335 0.00728 t 0.38458$	1.2	0.92451
		4.0	0.930002
		7.4	0.90728
RhB@HO-Ph-NH-MCM-41	$M t M ∞ = 0.14878 t 0.28038 0.09147 t 0.35298 0.00724 t 0.3755$	1.2	0.94581
		4.0	0.94221
		7.4	0.9177
RhB@HOOC-Ph-NH-MCM-41	$M t M ∞ = 0.2182 t 0.25951 0.14547 t 0.31183 0.00876 t 0.34229$	1.2	0.92259
		4.0	0.93739
		7.4	0.87306

表5 四种药物载体药物释放曲线拟合结果

Table 5 Results of drug release curve fitting of four drug carriers

载药载体	拟合方程	pH	相关系数R²
RhB@Me-Ph-NH-MCM-41	$M t M ∞ = 0.12461 t 0.26126 0.09507 t 0.29661 0.00050710 t 0.43314$	1.2	0.97413
		4.0	0.94715
		7.4	0.96264
RhB@OHC-Ph-NH-MCM-41	$M t M ∞ = 0.01585 t 0.307 0.12541 t 0.32335 0.00728 t 0.38458$	1.2	0.92451
		4.0	0.930002
		7.4	0.90728
RhB@HO-Ph-NH-MCM-41	$M t M ∞ = 0.14878 t 0.28038 0.09147 t 0.35298 0.00724 t 0.3755$	1.2	0.94581
		4.0	0.94221
		7.4	0.9177
RhB@HOOC-Ph-NH-MCM-41	$M t M ∞ = 0.2182 t 0.25951 0.14547 t 0.31183 0.00876 t 0.34229$	1.2	0.92259
		4.0	0.93739
		7.4	0.87306

图6 在pH = 1.2、pH = 4.0和pH = 7.4下四种载药载体累积释药曲线

Fig.6 Cumulative release drug curves of four drug carriers at pH = 1.2, pH = 4.0 and pH = 7.4

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NH₂-MCM-41的改性及其pH响应性释药的研究

Study on modification of NH₂-MCM-41 and its pH-responsive drug release

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