Multilayer microcapsules for delivery, control and triggered release of bioactive compounds

Abstract

Developing of targeted drug delivery systems is currently a very important topic, which can be easily judged by a great number of papers published every year. Materials science proposes, among others, microcapsules as one of the possible solutions to the problem. Known for more than a decade by know, microcapsules, their properties, methods of encapsulation, release, control where under thorough investigation by several scientific groups in the world. Despite the fact that many factors were already studied, application of this system to drug delivery provides an enormous amount of work yet to be done, lying across several areas of science – biology, chemistry, physics, medicine. To be used as a technique of targeted delivery, not only the microcapsules should meet many constraints on their physical and chemical properties, but also the means of their control and release triggering irradiation should be applicable and harmless to living body. This means, that there's a lot more to do than to encapsulate the substances of interest and make sure they stay inside the capsules. This is why this research was devoted to investigation of stability of cargo encapsulated to layer-by-layer microcapsules constructed on silica and CaCO3 microparticles using various shell constructions with synthetic and biodegradable polyelectrolytes, nanoparticles, DNA, enzyme and other materials, methods of microcapsules control by magnetic field, which can be used for navigation of the carriers in-vivo to the place of interest and methods of release of encapsulated substances from the microcapsules, that are friendly to living body. The thesis starts with introduction and a literature review to help reader to get a better understanding on the structures discussed in this work and what have already been done in the area. These are followed by a short description of main materials and methods used to conduct this research. Three following chapters of experimental section describe the research itself. Chapter 4 shows feasibility of triggered IR-laser and high-frequency ultrasound release, including intracellular release. Reporting application of cargo using pH-sensitve dye is shown. Ultrasoundtriggered release at parameters, close to that currently used in medical applications, is shown to achieve up to 60% efficiency of previously reported highpower 20 kHz ultrasonic irradiation. Feasibility of laser-induced triggered release using microcapsules functionalized photo-sensitive dyes was also shown. In Chapter 5 retention of activity of DNA and enzyme molecules upon encapsulation was demonstrated. Activity of encapsulated substances was shown to be lower, than of free ones, but the accessibility and kinetics of reactions can be controlled by adjusting the construction of microcapsules. In Chapter 6 feasibility of control of cells impregnated with microcapsules functionalized with magnetite nanoparticles was shown at distances of up to 10 mm using usual constant magnets.