Microfluidics Technology for the Design and Formulation of Nanomedicines

Abstract

In conventional drug administration, drug molecules cross multiple biological barriers, distribute randomly in the tissues, and can release insufficient concentrations at the desired pathological site. Controlling the delivery of the molecules can increase the concentration of the drug in the desired location, leading to improved efficacy, and reducing the unwanted effects of the molecules under investigation. Nanoparticles (NPs), have shown a distinctive potential in targeting drugs due to their unique properties, such as large surface area and quantum properties. A variety of NPs have been used over the years for the encapsulation of different drugs and biologics, acting as drug carriers, including lipid-based and polymeric NPs. Applying NP platforms in medicines significantly improves the disease diagnosis and therapy. Several conventional methods have been used for the manufacturing of drug loaded NPs, with conventional manufacturing methods having several limitations, leading to multiple drawbacks, including NPs with large particle size and broad size distribution (high polydispersity index), besides the unreproducible formulation and high batch-to-batch variability. Therefore, new methods such as microfluidics (MFs) need to be investigated more thoroughly. MFs, is a novel manufacturing method that uses microchannels to produce a size-controlled and monodispersed NP formulation. In this review, different formulation methods of polymeric and lipid-based NPs will be discussed, emphasizing the different manufacturing methods and their advantages and limitations and how microfluidics has the capacity to overcome these limitations and improve the role of NPs as an effective drug delivery system.

Keywords: PLGA; drug delivery; liposomes; microfluidics; nanomedicine; nanoparticles.

Figure 1

Thin film hydration method for empty liposome preparation. The liposomes produced from this method are often polydisperse; however, there is a correlation between the duration spent during the rotary evaporation step and the quality of thin film produced. Factors such as mixing speed and temperature after the hydration will also effect the quality of the liposomes so this must be monitored.

Figure 2

An illustration for the procedure of the solvent injection method to produce empty liposomes. The major factors to consider during the solvent injection method are the temperature during injection (as this will vary depending upon the phase transition temperatures of individual lipids), and the injection rate. These factors will affect the size, shape and polydispersity of the liposomes produced. A following method such as micro-extrusion is normally required after solvent injection to obtain a therapeutically viable formulation.

Figure 3

The preparation of liposomes by extrusion method using polycarbonate filters. Increasing the number of transitions through the membrane will reduce the polydispersity of the formulation. The process should also be performed at a temperature similar to that of the lipid transition temperature, to prevent lipid cleavage (and subsequent liposome breakdown) upon extrusion.

Figure 4

Schematic presentation of liposomes manufacturing using the microfluidic system. Figure adapted from Weaver et al. [152].