(3b) Composite Hydrogel Microparticles for Drug Delivery: Microfluidic Preparation, Antibody Functionalisation and Interaction with Cells

Authors: 
Pittermannova, A., University of Chemistry and Technology
Ruberova, Z., University of Chemistry and Technology
Lizonova, D., University of Chemistry and Technology
Majerska, M., University of Chemistry and Technology
Bremond, N., ESPCI ParisTech
Bibette, J., ESPCI ParisTech
Stepanek, F., University of Chemistry and Technology
Zadrazil, A., University of Chemistry and Technology
Hubatova Vackova, A., UCT Prague
This work presents composite hydrogel microparticles for drug delivery systems. Compartmentalised microparticles were synthesized from a calcium alginate gel matrix and contain several functional components, namely iron oxide nanoparticles for radiofrequency heating and MRI visualisation, liposomes for the storage and release of active molecules of their precursors, and optionally also immobilised enzymes that facilitate the conversion of pro-drugs to active substances. Liposomes are spherical structures formed by a phospholipid bilayer, which are able to release the active matter in response to temperature. The permeability of liposomes can be significantly increased once they are heated above its phase transition temperature. The needed temperature change is achieved by iron nanoparticles upon exposure to an external radio-frequency magnetic field.

Monodisperse microparticles with the required size were prepared by using microfluidic techniques. By implementing extractive gelation technique on the microfluidic chip, it was possible to produce highly monodisperse alginate microparticles in the size range of blood cells, which is important for the future intravenous application. Effects of several variables on the final size and morphology of microparticles were evaluated. The iron nanoparticles and liposomes were encapsulated. The stability of liposomes in the alginate microparticles was investigated and remotely triggered release experiments were conducted.

Due to high stability of final microparticles in a buffer solution, their surface modification was feasible. Different approaches to microparticles modification by IgG antibody were evaluated. The most appropriate technique was modification through chitosan previously attachted on the alginate microparticles. Lastly, experiments describing interactions of functionalised micropaticles with the cells were evaluated.