肠靶向海藻酸钙基微胶囊的制备及控释性能研究

doi:10.11949/0438-1157.20200418

摘要/Abstract

摘要：

利用毛细管共挤出技术结合静电吸附和仿生硅化的方法，制备了海藻酸钙-壳聚糖/精蛋白/二氧化硅(ACPSi)复合微胶囊。ACPSi复合微胶囊的平均粒径约3.18 mm，单分散性好，囊壁最外层的二氧化硅层可抑制其在肠液pH环境中的溶胀，增强囊的机械稳定性。将羟丙甲基纤维素邻苯二甲酸酯(HPMCP)肠溶微球作为释药“微阀门”，嵌入囊壁可以更好地控制微胶囊的释药行为。以吲哚美辛为模型药物，当药物浓度为22.5 mg/ml时，ACPSi载药微胶囊在pH 2.5模拟胃液中3 h时累计释药率仅为0.33%，而转移至pH 6.8模拟肠液中19 h时累计释药率为77.78%；囊壁嵌入HPMCP微球后，22 h时累计释药率可提高约4%。因此，该复合微胶囊具有良好的肠靶向作用和控释特性，作为口服肠靶向缓控释制剂具有良好的应用前景。

关键词: 微胶囊, 肠靶向, 控制释放, 海藻酸钙, 微流体学, 药物, 传质

Abstract:

Ca-alginate-chitosan/protamine/silica (ACPSi) composite microcapsules were prepared by using capillary coextrusion technology combined with electrostatic adsorption and bionic silicification. The prepared composite ACPSi capsules have good monodispersity and the average particle size is about 3.18 mm. The rigid outer silica layer of the microcapsules can effectively inhibit the capsule swelling at pH 6.8 to improve the mechanical stability of the microcapsules. In addition, drug release behavior of microcapsules can be further controlled by embedding HPMCP enteric microspheres into the shell of ACPSi capsules as “micro-valves”. When the concentration of indomethacin is 22.5 mg/ml, the cumulative release rate of the ACPSi capsules is 0.33% at pH 2.5 for 3 h, after transferring to pH 6.8 buffer solution for 19 h, the cumulative release rate reaches 77.78%. The cumulative release rate can be increased by about 4% when HPMCP microspheres embedded into the capsule shell. The proposed ACPSi composite capsules exhibit good intestinal-targeted controlled-release performance, which provides a new strategy for developing oral intestinal-targeted drug delivery systems.

Key words: capsules, intestinal-targeted delivery, controlled-release, Ca-alginate, microfluidics, pharmaceuticals, mass transfer

中图分类号:

TB 34

温霜, 巨晓洁, 谢锐, 汪伟, 刘壮, 褚良银. 肠靶向海藻酸钙基微胶囊的制备及控释性能研究[J]. 化工学报, 2020, 71(8): 3797-3806.

Shuang WEN, Xiaojie JU, Rui XIE, Wei WANG, Zhuang LIU, Liangyin CHU. Fabrication and controlled-release properties of intestinal-targeted Ca-alginate-based capsules[J]. CIESC Journal, 2020, 71(8): 3797-3806.

图/表 8

图1 利用毛细管共挤出装置制备ACPSi复合微胶囊的示意图(a)共挤出装置; (b)海藻酸钙-壳聚糖复凝聚; (c)精蛋白吸附; (d)仿生硅化; (e) AC微胶囊; (f) ACP微胶囊; (g) ACPSi复合微胶囊

Fig.1 Schematic illustration of the process for preparation of Ca-alginate-based capsules by co-extrusion device

图2 AC微胶囊与ACPSi微胶囊的光学照片[(a)~(d)]与粒径分布图[(e)、(f)]

Fig.2 Optical photos((a)—(d)) and size distributions ((e),(f)) of AC capsules and ACPSi capsules

图3 ACPSi微胶囊的SEM图[(a)~(c)]和EDX分析(d)

Fig.3 SEM images((a)—(c)) and EDX spectra(d) of ACSPSi capsule

图4 HPMCP微球在纯水中的光学显微照片(a)和SEM图(b)，以及HPMCP微球在pH 2.5和pH 6.8条件下的粒径变化(c)

Fig.4 Microscopical photo (a) and SEM image (b) of HPMCP microspheres in pure water, and size changes of HPMCP microspheres at different pH conditions (c)

图5 AC微胶囊和ACPSi微胶囊受到挤压时的应力-应变曲线(a)，ACPSi微胶囊开始受到挤压发生形变(b)和最终破裂(c)的照片(标尺为1 cm)

Fig.5 The stress-strain curves of AC and ACPSi capsules when they are extruded (a); the photos of ACPSi capsule starts to be squeezed (b) and finally burst (c)(the scale bar is 1 cm)

图6 AC和ACPSi微胶囊保存于0.2 mol/L醋酸溶液以及在不同pH条件下的粒径

Fig.6 Sizes of AC and ACPSi capsules in 0.2 mol/L acetic acid solution and under different pH conditions

图7 ACPSi载药微胶囊保存0.2 mol/L的醋酸溶液中含药量的变化

Fig.7 Changes in drug content of ACPSi capsules stored in 0.2 mol/L acetic acid solution

图8 不同载药浓度的ACPSi微胶囊在pH 2.5和pH 6.8条件下的释药曲线(IMC代表吲哚美辛)

Fig.8 Drug release curves of ACPSi capsules with different drug loading concentrations at pH 2.5 and pH 6.8(IMC is indomethacin)

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