Mesoporous SiO2-based membranes with variable pore structure, geometry and chemical surface modification, for fine-tuned drug loading and release properties in transdermal drug delivery

Transdermal drug delivery systems (TDDSs) play important roles in therapy due to distinct advantages over other forms and types of drug application. Despite being in clinical use since decades, TDDS have yet to reach their full potential. While polymer matrices are most commonly used as transdermal patches so far, inorganic carriers like mesoporous silica membranes offer several advantages, including high loading capacities, favorable physical, technical and biological properties as well as chemical and mechanical stability, offering possible re-use / drug re-loading and a broad chemical compatibility with drugs and chemical enhancers. Mesoporous glass membranes can be prepared in different monolithic shapes, with a particularly wide range of possible pore volumes, pore diameters, specific surface areas and chemical modifications. Here, we explored for the first time monolithic SiO2-based carriers as sustained release systems of therapeutics. In an ideally stirred vessel as model system, we systematically analyzed the influence of pore diameter, pore volume, and the dimensions of glass monoliths on the loading and sustained release of different drugs, including anastrozole, xylazine, imiquimod, levetiracetam, and flunixin. Additionally, we chemically modified high or low porosity mesoporous silica membranes by post-synthetic methods and compared the effects of different surface modifications on drug loading efficacies and release profiles. The systematic variation of the mesoporous glass membrane properties revealed pore volumes and drug concentrations, but not pore diameter or pore surface area as important parameters of drug loading and release kinetics. Other relevant effectors include the occurrence of lateral diffusion within the carrier and drug-specific properties such as adsorption. Additionally, drug loading capacities and release profiles were substantially affected by chemical surface modifications with strongly acidic SO3H groups or hydrophobic methyl groups, while introducing weakly acidic COOH groups or nitrile groups showed little effects. SO3H modification of low porosity (LP) membranes led to markedly increased loading capacity and a more sustained release profile of anastrozole. Increasing LP membrane hydrophobicity by methyl modification essentially abolished anastrozole drug loading. Biocompatibility studies showed full biocompatibility of SO3H functionalized membranes as indicated by efficient cell attachment and viability. These physical and chemical structure-property relationships will allow further fine-tuning of the systems according to their desired properties as TDDS, thus guiding towards optimized systems for use in transdermal drug applications.