一步法制备生物相容油核微胶囊及其可控释放

doi:10.11949/0438-1157.20201000

摘要/Abstract

摘要：

一步法可控制备生物相容油核微胶囊对工业制备微胶囊及其应用具有重要意义。通过设计微流控器件，成功实现一步法制备尺寸均一可控的生物相容油核微胶囊。利用玻璃毛细管管套管的方法制备了微流控器件。通过外相水凝胶相剪切内相油相得到油核液滴，同时油核液滴和外相水凝胶相在重力作用下脱离管口，形成油核微胶囊，再通过交联水凝胶壳层得到稳定的结构。系统研究了微流控器件结构、内相流速、外相流速等参数对油核微胶囊油核数量、微胶囊直径、壁厚等性质的影响规律。生物相容油核微胶囊作为活性物质的理想载体，可以实现pH改变触发的快速释放和壁厚调节的缓慢释放，为其实际应用奠定了基础。

关键词: 微流体学, 微胶囊, 生物相容, 可控释放, 功能载体, 微通道, 凝胶

Abstract:

One-step controlled preparation of biocompatible oil-core microcapsules is of great significance for the industrial fabrication of microcapsules and their applications. In this paper, biocompatible oil-core microcapsules with uniform and controllable size are successfully prepared via a one-step method using microfluidic devices. This method uses concentrically-aligned glass capillaries to prepare microfluidic devices. The inner oil phase is sheared into oil droplets by the outer hydrogel phase, which is then pulled off the orifice of the microfluidic device by gravity, forming oil-core microcapsules. The shells of the microcapsules are then cross-linked to form a stable hierarchical structure. The influences of microfluidic device design, inner phase and outer phase flow rates on the number of oil cores, microcapsules diameter and shell thickness are systematically investigated. As an ideal carrier for active substances, biocompatible oil-core microcapsules can achieve rapid release triggered by pH changes and slow release of wall thickness adjustment, laying the foundation for their practical applications.

Key words: microfluidics, microcapsules, biocompatible, controlled release, functional delivery vehicle, microchannels, gels

中图分类号:

TQ 021.4

石盼, 颜肖潇, 王行政, 冯乐耘, 陈东. 一步法制备生物相容油核微胶囊及其可控释放[J]. 化工学报, 2021, 72(1): 619-627.

SHI Pan, YAN Xiaoxiao, WANG Xingzheng, FENG Leyun, CHEN Dong. One-step fabrication of biocompatible oil-core microcapsules with controlled release[J]. CIESC Journal, 2021, 72(1): 619-627.

图/表 6

表1 内外相流体物性参数

Table 1 Physical properties of inner or outer fluids

	密度/(g/ml)	黏度/(mPa?s)	表面张力/(mN/m)
内相	0.88	6	35.3
外相	1.00	300	70.2

图1 玻璃毛细管微流控器件及其制备油核微胶囊:内管管口伸出外管管口的玻璃毛细管微流控器件(a)；微胶囊生成过程(b)；油核微胶囊(c)；制备微胶囊的相图(红色圈表示可以形成单核微胶囊，黑色叉表示无法形成微胶囊)(d)

Fig.1 Preparation of oil-core microcapsules by glass-capillary microfluidic device. Glass capillary microfluidic device with inner nozzle extending from outer nozzle(a). Microcapsule formation process (b). Oil core microcapsules(c). Phase diagram of the prepared microcapsules, the red circle indicates that mononuclear microcapsules can be formed, and the black cross indicates that microcapsules cannot be formed (d)

图2 内相流速和外相流速对油核微胶囊直径和壁厚的影响:内相流速对微胶囊直径和壁厚的影响，外相流速保持10 ml/h不变(a)；不同内相流速下生成的微胶囊实物图，外相流速保持10 ml/h不变(b)；外相流速对微胶囊直径和壁厚的影响，内相流速保持0.5 ml/h不变(c)；不同外相流速生成的微胶囊实物图，内相流速保持0.5 ml/h不变(d)；高速相机拍摄的微胶囊形成过程(e)

Fig.2 Effect of inter phase flow rate and outer phase flow rate on the diameter and wall thickness of the oil-core microcapsules. Effect of inter phase flow rate on the diameter and wall thickness of the microcapsules, external phase flow rate remains constant at 10 ml/h (a). The physical map of the microcapsules generated at different inter phase flow rates, external phase flow rate remains constant at 10 ml/h (b). Effect of external phase flow rate on the diameter and wall thickness of the microcapsules, inter phase flow rate remains constant at 0.5 ml/h (c). The physical map of the microcapsules generated at different external phase flow rates, inter phase flow rate remains constant at 0.5 ml/h (d). The formation process of microcapsules captured by a high-speed camera (e)

图3 玻璃毛细管微流控器件结构对油核微胶囊的影响:内管管口与外管管口平齐的玻璃毛细管微流控器件(a); 管口平齐微流控器件制备微胶囊的相图(b)；管口平齐微流控器件制备得到的多核微胶囊实物图(c)；内管管口缩进外管管口的玻璃毛细管微流控器件(d)；内管缩进外管微流控器件制备微胶囊的相图(e)

Fig.3 Effect of glass capillary microfluidic devices on the oil-core microcapsules. Glass capillary microfluidic device with inner tube orifice flush with outer tube orifice (a). Phase diagram of microcapsules prepared by microfluidic devices with flush nozzles (b). Physical image of multi-core microcapsules prepared by a flush nozzle microfluidic device (c). Glass capillary microfluidic device with inner tube orifice retracted into outer tube orifice (d). Phase diagram of microcapsules prepared by microfluidic device with inner tube retracted into outer tube (e)

图4 生物相容油核微胶囊的pH响应和快速释放:油核微胶囊的pH响应(a)；磷酸氢二钠激发油核微胶囊的快速释放(b)；柠檬酸钠激发油核微胶囊的快速释放(c)

Fig.4 pH-triggered fast release of oil cores from biocompatible microcapsules. pH response of oil core microcapsules (a). Dibasic sodium phosphate stimulates rapid release of oil core microcapsules (b). Sodium citrate stimulates rapid release of oil core microcapsules (c)

图5 油核微胶囊的缓慢释放: 不同壁厚油核微胶囊中活性物质的缓慢释放曲线(a)；不同壁厚油核微胶囊的实物图(b)

Fig.5 Sustained release of oil-core microcapsules. Sustained release curves of active substances in oil-core microcapsules with different wall thicknesses (a). Physical image of oil core microcapsules with different wall thicknesses (b)

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