Insight into charged drug release from metal-organic frameworks

The use of metal-organic frameworks (MOFs) as platforms in biological settings is an area in which they should shine, however, the adaptation of these materials in critical roles such as for drug delivery has been slow and limited. This can be attributed to the relative novelty of MOFs in the field and the lack of a comprehensive understanding surrounding how MOF components and solution conditions may influence release. In this work, we deliver broad view of how charged molecules are influenced by surrounding interactions to inform and improve drug release applications. To do this, a variety of MOFs [MIL-100, UiO-66, UiO-66-NH₂, UiO-66-NO₂, and UiO-66-OH] were synthesized to evaluate how the presence of functional groups and other electrostatic groups, like buffer molecules, ions, and polyelectrolytes, may influence loading and release of charged dye and drug models. To evaluate these results, we utilize the conventional Korsmeyer-Peppas (K-P) model which can inform us of the mechanisms of release. However, this and other models fail to adequately describe some of the biphasic release profiles observed. To overcome this hurdle, we present a novel adaptation of the K-P model by combining it with a burst release term while accounting for the proportion of release during each phase to describe the biphasic release observed. This allows for the extraction of empirical insights and the appropriate description of the mechanisms of release that would otherwise go unnoticed. In doing so, we reveal several phenomena present during release that can be used to better understand the process and can be leveraged to promote the controlled drug release of charged drug molecules.