Formation of nano- and micro-scale drug delivery systems using microfluidic technology

The recent developments in microfluidic technology have provided an effective microreactor platform for the production of a range of pharmaceutically related materials in both nano- and micro-scale. This can be attributed to the unique characteristics that microfluidic-based reactors offer in terms of controllability and uniformity of the material characteristics, compared to conventional batch reactors. In this article, the fundamental and practical advantages associated with microfluidic technology are discussed with specific examples presented for the formation of nano- and micro-scale drug delivery systems.

Microfluidics is a field of science and technology that deals with small volumes of fluid in the range of nanolitres to picolitres (i.e. 10^–9 to 10^–12 litres) which flows within micro-scale channel networks¹. The main feature of such microsystems is the miniaturisation of the fluidic environment, with a channel width of tens to hundreds micrometers (about the diameter of human hair), where chemical or biological samples are brought together, using a variety of pumping techniques, for reaction, separation and/or analysis. This scaling-down in operation space (compared to the conventional macro-scale flow system) not only reduces the fluid volume, but also brings unique characteristics into the microfluidic environment.  The unique operating characteristics include (i) a laminar flow environment where molecular diffusion dominates the mass transfer process, (ii) a high surface-area-to-volume ratio which makes surface effects become significant, and (iii) spatial and temporal control of fluids, especially the physical and chemical properties within the microenvironment². Therefore, microfluidics offers opportunities for research and development of new systems and processes with advantages in terms of speed, performance, integration, portability, sample/solvent quantity, automation, hazard control, and cost.

The chromatography-on-a-chip developed in 1979 at Stanford University was perhaps the first microfluidic system³. Over the last two decades, the development of microfluidic technology has witnessed an explosive growth and the applications have spread widely over diverse areas such as chemistry, physics, life sciences and biomedical engineering. In this article, the fundamental and practical advantages associated with microfluidic technology are discussed with specific examples presented for the formation of nano- and micro-scale drug delivery systems.

Formation of nanostructured drug delivery systems using microfluidic reactors

In nanotechnology-based formulations, polymeric micelles (PMs) possess a prominent position, which are self-assembling colloidal systems with block or graft amphiphilic copolymers as drug carriers. They are regarded as strong drug delivery candidates owing to (a) their nano-scale dimension that permits local administration, and (b) the presence of the polymeric shell that prolongs the in vivo bioavailability⁴. From the pharmacological point of view, the PMs core-shell structure is of particular interest for the aqueous environment where the hydrophobic blocks of the copolymer form the core of the micelles while the hydrophilic blocks form the corona or outer shell. The hydrophobic micelle core serves as a microenvironment for the incorporation of hydrophobic drugs, while the corona shell serves as a stabilising interface between the hydrophobic core and the external medium (Figure 1a). Since most of the pharmaceutically active organic compounds are hydrophobic, poorly soluble in water, or even water-insoluble, polymeric micelles provide a promising platform to overcome the solubility issue⁵.