Novel nanoporous SiO2-based flexible foils and textiles as sustained release systems for the transdermal application of drugs

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Transdermal application systems (transdermal drug delivery systems, TDDS) already play important roles in pharmacotherapy. Advantages are, among others, the sustained/controlled release of drugs with concomitantly more even blood levels over longer time periods as well as improved biocompatibility (avoiding concentration peaks), efficacy (longer maintenance of therapeutic drug levels in the blood), and compliance. The exploitation of the full potential of TDDS, however, requires the development of novel systems, with broader applicability for various drugs, solvents and chemical enhancers, and with advantageous physical, technical and biological properties.This project aims at the exploration of porous silica bodies for the first time, which are characterized by remarkable compatibility with solvents/chemical enhancers, applicability for a broad spectrum of drugs for loading, very systematically modifiable release kinetics, broadly variable pore sizes and tortuosities as well as stability and reusability through repetitive loading and release. The generation of these systems is a core competence of the Enke group, which in project-relevant preliminary work already established porous glasses as flat plates or foils. Project-relevant preliminary studies by the Aigner group already generated adhesive TDDS for anastrozole, prior to testing them in vitro and preclinically in vivo. In contrast to these TDDS relying on a silicon matrix, however, the nanoporous SiO2-based systems of this project demonstrate substantially improved properties, thus qualifying them for further development and exploration for anastrozole and other drugs.For the first time, nanoporous SiO2-based glass bodies with very flexible pore structure and geometry (pore size, pore volume, tortuosity, outer morphology) will be systematically developed and established as sustained release systems for transdermal application of drugs. These will be loaded with different, pharmacologically relevant drugs, which differ regarding hydrophobicity/hydrophily and medical applications. Based on structure-activity relationships, pore sizes and -architectures will be systematically optimized and additional surface functionalization will be implemented. Thin porous glass plates identified as optimal will then be comprehensively characterized with regard to their interaction with biological materials, toxic effects and physical properties. These results will provide the basis for the subsequent generation of novel textiles based on porous glass fibers as well as partially or fully porous flexible glass foils. For optimal systems, in vivo studies in rats will be performed for analyzing pharmacokinetics of released drugs. The goal of this project is thus the development of novel sustained release systems with improved physical/chemical, biological and pharmaceutical/ pharmacological properties.