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

经皮给药系统（transdermal drug delivery systems，TDDS）在药物治疗中已经发挥了重要作用。优点尤其是药物的持续/控制释放，伴随着更长时间内更均匀的血液水平以及改善的生物相容性（避免浓度峰值）、功效（血液中治疗药物水平的更长维持）和顺应性。然而，充分开发TDDS的潜力需要开发新的系统，对各种药物，溶剂和化学增强剂具有更广泛的适用性，并具有有利的物理，技术和生物学特性。本项目旨在首次探索多孔二氧化硅体，其特征在于与溶剂/化学增强剂具有显着的相容性，用于装载的广谱药物的适用性、非常系统地可改变的释放动力学、广泛可变的孔径和弯曲度以及通过重复装载和释放的稳定性和可重复使用性。这些系统的产生是Enke集团的核心竞争力，在项目相关的前期工作中，已经将多孔玻璃确定为平板或箔。艾格纳小组的项目相关初步研究已经产生了阿那曲唑的粘附TDDS，然后在体外和临床前体内进行测试。然而，与这些依赖于硅基质的TDDS相比，该项目的基于纳米多孔SiO2的系统表现出显著改善的性质，从而使它们有资格用于阿那曲唑和其他药物的进一步开发和探索。将系统地开发和建立用于药物经皮应用的缓释系统（孔径、孔体积、曲折度、外部形态）。这些将装载有不同的、与药物相关的药物，这些药物在疏水性/疏水性和医学应用方面不同。基于结构-活性关系，孔径和结构将被系统地优化，并将实施额外的表面功能化。然后，将对确定为最佳的薄多孔玻璃板与生物材料的相互作用、毒性效应和物理特性进行全面表征。这些结果将为后续一代基于多孔玻璃纤维以及部分或完全多孔柔性玻璃箔的新型纺织品提供基础。对于最佳系统，将进行大鼠体内研究，以分析释放药物的药代动力学。因此，该项目的目标是开发具有改进的物理/化学、生物学和药学/药理学特性的新型缓释系统。

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.