Hybrid Microgels

Drug delivery for the treatment of chronic diseases relies on the effective delivery of payload materials to target cells during long-term release. Hybrid microgels prepared by droplet microfluidic technology can be used as an effective platform for drug delivery using macroscopic and nano-encapsulated systems.

Why Are Hybrid Microgels An Ideal Carrier?

In order to continuously improve drug release in drug therapy, one of the methods is to incorporate nanoparticles or small drugs into the porous matrix of the hydrogel, where the required payload can be continuously captured and released. At present, due to its inherent biocompatibility, low level of cytotoxicity, and other advantages, alginate (ALG) hydrogels have been widely studied as a platform for macro and microencapsulation. However, with changes in pH and temperature, the instability of the ALG hydrogel may occur uncontrollably, which may result in the loss of divalent ions. At the same time, due to its hydrophilicity, the ability to load hydrophobic drugs is very low.

Structure of hybrid microgels.

Figure.1 Structure of hybrid microgels. (Carvalho B. G, et al. 2021)

In order to overcome these shortcomings, the formation of hybrid hydrogels has been promoted as a strategy to improve the physical and chemical properties of the only ALG hydrogel. Other biopolymers have been used to adjust the degradation time of the porous alginate matrix, among which silk fibroin (SF) and chondroitin sulfate (CS) both stand out due to their natural interactions with hydrophobic and hydrophilic molecules, respectively.

Hydrogels using CS, SF and ALG blends have been proposed as an alternative to incorporation/release of required payloads, which can be used to construct micro-scale carriers for drug release or extracellular incorporation of nanoparticles.

Hybrid Microgels in Microfluidic Devices

The mechanism of droplet breaking can be used to realize the preparation of monodisperse hydrogel beads. The two immiscible liquid phases meet at the junction of the microfluidic chip. Here, the local flow field causes the droplets to shrink in a reproducible manner, resulting in droplets of precise and adjustable size. The subsequent gelation or solidification of the droplets results in the formation of hydrogel beads.

We use standard soft lithography techniques to prepare microfluidic devices in PDMS with a PDMS/initiator ratio of 10:1. The device is combined with the glass through O2 plasma surface activation and treated with Aquapel to keep the glass surface hydrophobic and increase the wettability of the oil. The hydraulic focusing device consists of two different inlet phases (dispersed and continuous) to form monodisperse emulsion droplets with widths of 30 μm and 20 μm, respectively.

Droplet-based microfluidic device template used to obtain ALG microgels.

Figure.2 (A) Droplet-based microfluidic device template used to obtain ALG microgels. (B) Micrograph of collected microgels suspended in oil with fluorosurfactant. (C) Micrograph of microgels resuspended in water after oil and surfactant removal. (Carvalho B. G, et al. 2021)

In the hydrodynamic focusing droplet microfluidic device, ALG/SF/CS hybrid particles are prepared by internal gelation by the CLEX method. One of the inlets is composed of Ca-EDTA, alginate and fluorescently labeled polystyrene nanoparticles with a diameter of 0.1 μm, with a mass ALG/NP ratio of 10:1 (w/w). The second inlet stream consists of Zn-EDDA, alginate and second or third biopolymer (CS and/or SF). After production, a demulsifier is used to flush the micro-droplets and microgels, which are used to remove surfactants, causing emulsion breakage and droplet recovery.


  • Carvalho B. G, et al. (2021). "Hybrid Microgels Produced via Droplet Microfluidics for Sustainable Delivery of Hydrophobic and Hydrophilic Model Nanocarriers." Materials Science and Engineering: C. 118: 111467.

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