Chemical surface modification of mesoporous SiO2-based membranes for fine-tuning of drug loading and release properties

Abstract

Transdermal Drug Delivery Systems (TDDS) show significant advantages over other forms of drug application. Despite their clinical use for decades, these drug delivery devices 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 chemical stability and their tunable porous system, with adjustable pore sizes, pore volumes and surface chemistries. In this study, we chemically modified high and low porosity mesoporous silica membranes by post-synthetic methods and compared the effects of different surface modifications on loading efficacies and release profiles of different pharmacologically relevant drugs with different chemical properties. Drug loading capacities and release profiles were substantially affected by pore structure and surface modifcations with strongly acidic SO3H groups or hydrophobic methyl groups, while 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. The latter was also observed for xylazine, but associated with lesser drug loading. Likewise, the SO3H modification also slowed down the release of imiquimod or flunixin. Increasing LP membrane hydrophobicity by methyl modification essentially abolished anastrozole drug loading. In high porosity (HP) membranes, effects of chemical surface modifications were overall weaker. This led to particularly slow anastrozole or xylazine release profiles from methyl-modified membranes. Biocompatibility studies showed some cell-inhibitory effects of CN functionalization, but full biocompatibility of SO3H functionalized membranes as indicated by efficient cell attachment and high viability. Both parameters, pore structure and chemical surface modifcations, drug-dependently affect drug loading and release properties. Since they can be precisely fine-tuned in mesoporous silica membranes, this allows for the development of optimized TDDS providing high drug loading and the desired release profile of a given drug. Our results presented here indicate that the SO3H modification is particularly useful in this regard.