microASSIST: microfluidics to produce drug-loaded microspheres for cell therapy

poly(lactic-co-glycolic acid) or PLGA is an FDA approved polymer which is already used in a wide variety of therapeutic devices. The ratio in which lactic acid an glycolic acid are used to form the polymer greatly determines its physicochemical properties, and can be altered to suit the use. Further modifications can be added to optimize the polymer to the specific use case. Thus the versatile composition of PLGA makes it suit a wide range of specific applications. On top of that the biocompatibility and biodegradability make PLGA is an advantage for clinical applications.
Some diseases benefit from a slow release of the drug to prolong its therapeutic effect. This can be achieved in different ways, but a systemic release of the drug is almost always present and can be damaging in some cases, or exclude some drugs from being administered in a slow release form. A local slow release is therefore desired. PLGA is a promising candidate to fulfill this need, as we are able to encapsulate drugs in PLGA microspheres to have a local slow release application.
We are currently comparing two production methods to make these microspheres. First the conventional solvent extraction method with a rotor mixer and second a microfluidics setup which uses co-flow to produce particles. The main difference between both setups is the size of the particles produced. With the conventional method polydisperse particles (1-20µm) are produced, whereas with the microfluidics setup monodisperse particles (ca. 30µm) are obtained. Comparing both groups of particles in terms of release kinetics, ζ-potential, biodegradation,… should indicate the advantage of these monodisperse particles, as each particle has very similar properties compared to a polydisperse set. Furthermore we are also working on upscaling the production of monodisperse particles to suit industrial applications.
The disease model in which we will compare both sets of particles is β cell transplantation in type 1 diabetes. Here we have identified that glucocorticoids have a beneficial effect on the proliferation of β cells alongside the anti-inflammatory effect of glucocorticoids. The goal is to load glucocorticoids in PLGA microspheres and study the effect on the β cells in vitro (toxicity, viability, proliferation ,…) and in vivo (anti-inflammatory effect, graft survival, proliferation,…). Also collaborations with research groups focusing on other disease models, where local slow release of an anti-inflammatory agent are beneficial, are pending (ex. Arthritis). In a later stage loading the particles with other drugs and test them in other disease models should further increase the potential of this therapeutic approach.