Chitosan microcapsules production

In this Application Note, chitosan-shell/oily-core microcapsules are generated using the Raydrop double emulsion chip, 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.

We truly want to thanks our partner Secoya for the collaboration in the Application Note




Over the past few decades, core-shell microcapsules have been extensively used for the delivery and release of materials in the pharmaceutical, cosmetic, and food industries Microcapsules consisting of a chitosan shell and an oily core have been extensively studied as chitosan exhibits numerous benefits. These include: excellent biological activity, good biocompatibility and biodegradability and pH sensitivity for acid-triggered oral delivery. Traditional microencapsulation methods require complex processes and equipment and are difficult to control the size and load of the microcapsules. Microfluidics allows for the production of monodisperse double emulsions with a high level of control over both the size and the structure.



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.

Materials chitosan
Figure 2: Commplex Emulsions Production Platform
Figure 3: Experimental set-up to produce double emulsion

System components


Core phase:
Soybean oil (8001-22-7, Sigma-Aldrich) containing red dye Sudan IV (Sigma-Aldrich)

Shell phase:
Water containing 2% chitosan (viscosity 30-100 mPa·s, Glentham Life Sciences UK), 2% acetic acid (Sigma-Aldrich), 1% Pluronic® F-127 (Sigma-Aldrich)

Continuous phase:
1-octanol (Glentham Life Sciences UK) containing 2% Span 80 (Sigma-Aldrich)

Collection phase:
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). Except from this scenario, maximum working pressure is 1650 mbar. Priming and cleaning steps can require a pressure higher than 2 bar.

Synthesis of chitosan capsules

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.

Figure 4: Generation of double emulsion droplets  in the Raydrop. Red dye Sudan IV is added in the core phase  to increase the contrast.
Figure 5: chitosan-shell/oil-core double emulsion collected in the 1-octanol continuous phase

2. Capsule 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.


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 capsules as a function of time

Influence of the middle phase flow rate

After analyzing the size of the capsules 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.

Figure 8: Core size and shell size as a function of the shell liquid flow rate
Figure 9: Thickness of the shell as a function of the shell liquid 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


We 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 [3] as well as specific drugs, which will be delivered according to the pH acidity [2].


[1] KILDEEVA, N. R., PERMINOV, P. A., VLADIMIROV, L. V., NOVIKOV, V. V. and MIKHAILOV, S. N., 2009. About mechanism of chitosan cross-linking with glutaraldehyde. Russian Journal of Bioorganic Chemistry. 1 May 2009. Vol. 35, no. 3, p. 360–369. DOI 10.1134/S106816200903011X.

[2] 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.

[3] 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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