Microfluidic Drug Delivery Systems

In terms of precise delivery and handling of liquids, microfluidics has shown excellent prospects, which has gained great attention in the manufacturing of more effective drug delivery systems. One of the main applications of microfluidics, or the lab-on-a-chip can provide a platform for drug synthesis and delivery, which is crucial.

Besides, the use of microfluidic devices for drug administration has other advantages, such as reducing pain and reducing side effects. In addition to the above advantages, microfluidics also brings further improvements in cost, safety, and portability. This review will discuss the application of microfluidics in drug delivery.

Microfluidic Drug Carrier

Microfluidic technology provides a variety of methods to produce drug carriers.

• Spherical microcarriers: Droplet microfluidics is a powerful tool for producing monodisperse particles, microbubbles, as well as microgels. These microcarriers can be generated at kHz frequencies to encapsulate the desired compound, and the characteristics of the droplets can be adjusted to suit the specific requirements of the drug.
• Non-spherical particles: Microfluidic techniques for generating non-spherical drug carriers have gained attention.
• Self-assembly: Self-assembly technology is usually used to produce nano- to micron-sized drug carriers. Compared with the other two methods, self-assembly usually produces a smaller drug carrier.

Drug delivery at The Cellular Level

Microfluidics can be used to study the effects of certain drugs at the cellular level in various physical and chemical microenvironments. Microfluidics allows precise and controlled drug flow to the culture chamber to monitor, for example, the response of cells to high concentrations or to other biochemical stimuli. Microfluidic gradient generators (MGG) have been used to test cell-based drug responses. These devices have multiple advantages: higher resolution, real-time observation, adjustable drug concentration, and reduced costs.

Fig.1 Microfluidic gradient generators. (Lee K, et al. 2009)

MGG is mainly based on two technologies: the gradient is achieved through time-varying diffusion or parallel flow mixing.

• The first type of equipment usually has two containers in which one or more reagents of high concentration and low concentration are stored. These chambers are connected by a bridge, which may have a built-in valve in which cell culture is usually performed.
• The second type of MGG uses parallel flow to continuously flow inside the microfluidic device to generate a stable concentration gradient, which is suitable for long-term cell observation. The most common type is the tree gradient generator (TLGG).

Microfluidic Transdermal Drug Delivery

From the perspective of the whole organism, the most effective drug management method is still injection. Microfluidic chips for skin drug administration usually use microneedles to improve the delivery effect and reduce the pain associated with administration.

Solid Microneedle	Sharp solid microneedles can be used to puncture the skin. Because of their small size, they only cause minimum pain. After insertion, the needle can be withdrawn, and then the drug preparation can be applied to the punctured skin together with the drug-loaded patch or semi-solid preparation.
Hollow Microneedle	In a hollow microneedle, the drug is injected or diffused into the skin through a channel built into the microneedle. The advantage of having multiple hollow microneedles on a single device is that the liquid formulation can be delivered to a larger area, so that intradermal delivery can be faster.
Coated Microneedles	These microneedles use water-soluble preparations of drugs to achieve coating before administration. After piercing the skin, the drug dissolves into the skin. Common methods are aqueous solution dipping and spraying.
Dissolvable Microneedles	This type of microneedle is made of a soluble or biodegradable polymer that will completely dissolve after being inserted into the skin, thereby releasing the therapeutic agent encapsulated in it. Common manufacturing techniques rely on in-situ polymerization using micro molds or liquid monomers. The time the needle stays on the skin is closely related to the design and material of the device.

Fig.2 Schematic of a dissolvable MN patch mediating transdermal delivery of living and biofunctional probiotics. (Chen H. J, et al. 2018)

Implanted Microfluidic Drug Delivery Devices

Most microfluidic systems in drug delivery are diffusion-based devices. Depending on the diffusion coefficient of the drug, the use of a separate reservoir can continuously release the drug over a longer period of time. These devices are especially used in special areas such as the brain or eyes, where they can be implanted to actively deliver drugs in situ. The driving of these devices can be manual and can be performed by applying a voltage or a magnetic field.

Organs-on-a-Chip

Another important application of microfluidics is organs-on-a-chip. Researchers have successfully constructed microfluidic devices that can mimic the entire biological system, which can replicate the microenvironment of internal organs, thereby providing a low-cost preclinical testing platform for research. Multi-chamber microfluidic-based devices can be used to enhance the drug development process.

References

• Lee K, et al. (2009). "Generalized Serial Dilution Module for Monotonic and Arbitrary Microfluidic Gradient Generators." Lab Chip. 9: 709-717.
• Chen H. J, et al. (2018). "Transdermal Delivery of Living and Biofunctional Probiotics through Dissolvable Microneedle Patches." ACS Appl. Bio Mater. 1(2): 374-381.

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