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

透皮给药系统（透皮给药系统，TDDS）已经在药物治疗中发挥了重要作用。优点之一是药物的持续/控制释放，同时在更长的时间内具有更均匀的血液水平，以及改善的生物相容性（避免浓度峰值），功效（在血液中治疗药物水平的维持时间更长）和顺应性。然而，要充分发挥TDDS的潜力，就需要开发新的系统，这些系统对各种药物、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、技术和生物特性。该项目旨在首次探索多孔硅体，其特点是与溶剂/化学增强剂的良好相容性，适用于广泛的药物负载，非常系统地修改释放动力学，广泛可变的孔径和弯曲度，以及通过重复加载和释放的稳定性和可重用性。这些系统的产生是恩科集团的核心竞争力，该集团在项目相关的初步工作中已经建立了多孔玻璃作为平板或箔片。Aigner小组进行的与项目相关的初步研究已经为阿那曲唑产生了黏附的TDDS，然后进行了体外和临床前体内测试。然而，与这些依赖于硅基体的TDDS相比，该项目中基于纳米多孔sio2的系统表现出了显著改善的性能，从而使它们有资格进一步开发和探索阿那曲唑和其他药物。纳米多孔sio2基玻璃体具有非常灵活的孔隙结构和几何形状（孔径、孔体积、弯曲度、外部形态），将首次被系统地开发和建立为药物透皮缓释系统。这些将装载不同的药理学相关药物，这些药物在疏水性/亲水性和医学应用方面有所不同。基于结构-活性关系，孔径和结构将被系统地优化，并实现额外的表面功能化。确定为最佳的薄多孔玻璃板，然后将全面表征其与生物材料的相互作用，毒性作用和物理特性。这些结果将为下一代基于多孔玻璃纤维的新型纺织品以及部分或完全多孔柔性玻璃箔提供基础。为了优化系统，将在大鼠体内进行研究，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、生物和药物/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.