Abstract :
[en] Drug-loaded microspheres based on biocompatible and biodegradable polymers, mainly aliphatic polyesters, have demonstrated an increasing interest for producing devices with controlled or sustained release profiles of an active ingredient. They rely on the availability of scalable and robust production techniques. Microfluidic technology meets all these requirements and is characterized by high drug encapsulation efficiency and low particles size dispersity. As a result, this formulation process will become increasingly important in the near future for producing commercially available drug delivery systems even though optimizing the formulation process can be time-consuming.
Various microspheres parameters, such as size, polydispersity, composition, structure and shape, have a significant influence on drug release kinetics. The microfluidic technique enables precise control of these parameters which is essential for sustained and predictable drug-release. To modulate the release profile of microfluidically-formulated polylactide (PLA) microspheres, the incorporation of a more hydrophilic polyphosphoester (PPE) component was investigated. On the one hand, a PLA-PPE block copolymer was used as an additive to the polyester microsphere matrix. On the other hand, core-shell microspheres were formulated by adapting the microfluidic chip, enabling a PLA core to be coated with a layer of photo-crosslinked PPE. The impact of this PPE component and its localization on the encapsulation and release profile of model molecules was studied.
The developed microfluidic technologies were further used to produce poly(-caprolactone) (PCL) microspheres with shape memory properties. Two types of shape-memory microspheres were designed: (i) a PCL core coated with a crosslinked shell of PPE, and (ii) photo-crosslinked functionalized-PCL microspheres. For both systems, the stimulus for triggering shape memory is temperature (Tm (PCL) ≈ 45°C), which is not always suitable for biomedical applications. To overcome this limitation, a poly(ethylene oxide) (PEO) component was incorporated into PCL to form a hybrid network. In this way, shape memory can be triggered at room temperature by simple immersion in an aqueous medium.
