Design and fabrication of remotely controlled microcapsules for on- demand synthesis and release of unstable actives
April 3-7, 2016
The ability to control the rates of chemical or biochemical reactions at length-scales comparable to those of single-cell organisms or their sub-cellular compartments would be desirable in a number of situations, ranging from fundamental studies of transfer phenomena to applications such as controlled delivery of actives from functional materials in the pharmaceutical, food, personal care or crop protection products. Established strategies for the control of chemical reactions known from the macroscopic world, such as control of temperature, the addition rate of reactants, or the availability of a catalyst have been applied to autonomous micro-scale systems called “chemical robots”. A chemical robot is an internally structured microcapsule consisting of a semi-permeable membrane that regulates molecular transport between the interior and the surroundings, contains a system of stimuli-responsive internal compartments that store and release reactants, immobilised enzymes or catalysts for facilitating chemical reactions, and magnetic nanoparticles that act as susceptors and enable the receiving of remotely sent radiofrequency signals.
The talk will present an implementation of chemical robots based on soft hydrogel microcapsules produced by two methods: the drop-on-demand inkjet printing method , and a microfluidic flow-focusing chip. The advantages and disadvantages of each method will be discussed. Internal storage reservoirs were formed by phospholipid vesicles (liposomes) and an immobilised enzyme (laccase) was used as a biocatalyst. Super-paramagnetic iron oxide nanoparticles that dissipate heat when exposed to alternating magnetic field in the radiofrequency range were used as susceptors that facilitate the control of local temperature, which in turn controls the diffusion rate of reactants from liposomes and thus the local reaction rate . The talk will cover the fabrication methods for the bottom-up assembly of chemical robots with a special focus on repeatability and scalability, as well as the structural and functional characterization of the formed composite microcapsules. Several controlled release scenarios will be presented, including simple one-off release of a pre-synthesised chemical payload, repeated on/off release, and finally repeated starting, stopping and restarting of a local chemical reaction that produces a chemically unstable product . The first unstable product is a reactive oxygen species (ROS), which is shown to be a powerful cancerostatic agent using a 2D and 3D cell culture. The second unstable product whose on-demand production was demonstrated is allicin, a powerful naturally occurring antibiotic. The flow and deposition of chemical robots in porous media observed by MRI in the context of spatially specific delivery of actives will also be discussed .
 Haufová P., Dohnal J., Hanuš J., Štěpánek F., “Towards the inkjet fabrication of artificial cells”, Coll. Surf. A 410, 52-58 (2012)
 Hanuš J., Ullrich M., Dohnal J., Singh M., Štěpánek F., “Remotely controlled diffusion from magnetic liposome microgels”, Langmuir 29, 4381-4387 (2013)
 Ullrich M., Hanuš J., Štěpánek F., “Remote control of enzymatic reaction in compartmentalized microparticles: a system for the delivery of unstable actives”, Chem. Eng. Sci. 125, 191-199 (2015)
 Sarvašová N., Ulbrich P., Tokárová V., Zadražil A., Štěpánek F., “Artificial swarming: towards radiofrequency control of reversible micro-particle aggregation and deposition”, Powder Technol. 278, 17-25 (2015)
Frantisek Stepanek, Jaroslav Hanus, Monika Majerska, Anna Pittermannova, and Martin Jakubec, "Design and fabrication of remotely controlled microcapsules for on- demand synthesis and release of unstable actives" in "Design and Manufacture of Functional Microcapsules and Engineered Products", Chair: Simon Biggs, University of Queensland (Aus) Co-Chairs: Olivier Cayre, University of Leeds, UK Orlin D. Velev, North Carolina State University, USA Eds, ECI Symposium Series, (2016). http://dc.engconfintl.org/microcapsules/31