Microfluidic Chitosan Microcapsules Production
Microcapsules with a chitosan shell and an oily core have been extensively researched in recent years due to their biocompatibility and non-toxic biopolymer. In this application note, chitosan-shell/oily-core microcapsules are generated using the Raydrop double emulsion- developed and manufactured by Secoya and Fluigent pressure-based flow controllers. The influence of the fluidic parameters on the size and the release from the oil across the shell are studied and presented.
Secoya developed and manufactured the RayDrop used to perform this application note.
Over the past few decades, core-shell microcapsules as chitosan microcapsules have been extensively used for the delivery and release of materials in the pharmaceutical, cosmetic, and food industries.
Biopolymeric chitosan is considered as a promising encapsulating agent for textile applications due to its biocompatibility, lack of toxicity, antibacterial activity, high availability, and low cost. It’s considered nature’s most important organic compound after cellulose. Also, chitosan has unique chemical properties due to its cationic charge in solution.
Microencapsulation technologies play an important role in protecting the trapped material and in the durability of the effect, controlling the release rate.
Traditional microencapsulation methods require complex processes and equipment and are difficult to control the size and load of the microcapsules. Microfluidics enables the production of monodisperse double emulsions with a high level of control over both the size and the structure.
Chitosan microcapsules have been widely used as an encapsulating agent for several applications, such as food processing, biomedical and pharmaceutical, wastewater treatments, and textiles, alone or in combination with other polysaccharides or proteins to improve the shell properties. The application of chitosan microcapsules in textiles follows the current interest of industries in functionalization technologies that give different properties to products, such as aroma finish, insect repellent, antimicrobial activity, and thermal comfort.
Chitosan Microcapsules Generation: Materials
Setup for chitosan microcapsules generation
The production of droplets has been performed with the Complex Emulsions Production Platform, a lab system integrating all the components needed to produce simple and double emulsions.
Chitosan Microcapsules Generation system components
Soybean oil (8001-22-7, Sigma-Aldrich) containing red dye Sudan IV (Sigma-Aldrich)
Water containing 2% chitosan (viscosity 30-100 mPa·s, Glentham Life Sciences UK), 2% acetic acid (Sigma-Aldrich), 1% Pluronic® F-127 (Sigma-Aldrich)
1-octanol (Glentham Life Sciences UK) containing 2% Span 80 (Sigma-Aldrich)
Heptane (VWR) containing 2% Span 80 (Sigma-Aldrich) and 0,3 wt% glutaraldehyde (50% in H2O, Glentham Life Sciences UK)
The pressure controllers used are 7 bar full scale. The maximum pressure used for the generation of double emulsions with large shells is 2440 mbar (corresponding to a shell phase flow rate of 24.3 µL/min). Though in this scenario, maximum working pressure is 1650 mbar. Priming and cleaning steps can require a pressure higher than 2 bar.
Synthesis of chitosan microcapsules
Monodisperse chitosan microcapsules synthesis is performed in 2 main steps:
- Generation of monodisperse double emulsion in the Raydrop
- Capsule formation by reticulation of the chitosan shell in the collection bath
1. Double Emulsion Generation
To generate droplets, the system must first be primed with pure solvent in the shell phase (here water + 2% acetic acid). Once droplet formation is stable, the shell phase is switched to the chitosan-based solution. This avoids clogging issues during the transient phase.
2. Chitosan Microcapsules Formation
After generation, the droplets are collected in a cross-linking solution of 0.3% glutaraldehyde in hexane. The chitosan reacts with glutaraldehyde by solvent extraction and chemical cross-linking based on the Schiff base reaction. The droplets are solidified and become glutaraldehyde cross-linked chitosan microcapsules.
Figure 6: Glutaraldehyde cross-linked chitosan microcapsules on the cross-linking bath. On the left, after 4 minutes in the cross-linking bath. On the right, after 1h in the cross-linking bath. The shell thickness decreases and becomes progressively yellow, as a part of its water content diffuses in the continuous phase. Expelled water is clearly visible wetting the capsules.
Chitosan Microcapsules Production: Results
In this application note, different parameters were studied. First, the evolution of the droplets over time was observed. Then, the influence of the middle and the outer phase flow rates were studied.
Evolution of the Droplet Diameter During the Cross-Linking Process
After generation, the double emulsion droplets are collected into the collection solution. For a given sample, several measurements of the capsule diameter are done at different times. The evolution of the diameter is highlighted in Figure 7.
Figure 7: Size of chitosan microcapsules as a function of time.
Influence of the Middle Phase Flow Rate
After analyzing the size of the chitosan microcapsules over time, the influence of the middle phase flow rate is observed. We varied the shell flow rate at fixed continuous and core phase flow rates. The evolution of these two diameters is underlined in Figure 8. Figure 9 shows the evolution of the thickness of the droplet with the evolution of the shell flow rate.
Influence of the Outer Phase Flow Rate
Here, the shell flow rate and core flow rate are fixed but the continuous phase flow rate is varying. The change in diameter as a function of flow rate is shown in Figure 10.
Figure 10: Core size and shell size as a function of the outer liquid flow rate
The production of stable, monodispersed microcapsules with a solid chitosan shell and a liquid oil, non-polar core using a microfluidic system has been successfully achieved. The Fluigent microfluidic platform also allows one to tune the core diameter and the shell thickness by adjusting the flow rates of the different fluids. Due to excellent oil encapsulation properties and a very limited leakage over time, these microcapsules can be used in a wide range of applications, including the encapsulation of volatile products like mint oil  as well as specific drugs, which will be delivered according to the pH acidity .
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 LIU, Li, YANG, Jian-Ping, JU, Xiao-Jie, XIE, Rui, LIU, Ying-Mei, WANG, Wei, ZHANG, Jin-Jin, NIU, Catherine Hui and CHU, Liang-Yin, 2011. Monodisperse core-shell chitosan microcapsules for pH-responsive burst release of hydrophobic drugs. Soft Matter. 3 May 2011. Vol. 7, no. 10, p. 4821–4827. DOI 10.1039/C0SM01393E.
 DU, Yuhan, MO, Liangji, WANG, Xiaoda, WANG, Hongxing, GE, Xue-hui and QIU, Ting, 2020. Preparation of mint oil microcapsules by microfluidics with high efficiency and controllability in release properties. Microfluidics and Nanofluidics. June 2020. Vol. 24, no. 6, p. 42. DOI 10.1007/s10404-020-02346-2.
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