Influence of β-cyclodextrin on the release mechanism of genistein from poly(vinyl alcohol) matrices

Genistein (GEN), a naturally occurring isoflavone classified as a BCS Class II compound, has been shown to exhibit promising neuroprotective activity. However, this compound suffers from extremely poor aqueous solubility and low oral bioavailability. In order to overcome these limitations, GEN was encapsulated within β-cyclodextrin (β-CD) - selected on the basis of quantum-chemical modelling of geometric complementarity - and the resulting inclusion complex was incorporated into a polymer matrix (poly(vinyl alcohol) (PVA)). The stoichiometry and equilibrium constants of the GEN-α-CD, GEN-β-CD and GEN-γ-CD inclusion complexes were determined in DMSO in both the electronic ground and excited states using steady-state UV-Vis absorption, fluorescence and ¹H NMR spectroscopic techniques. The structural characterization of the ternary PVA-GEN-β-CD system was performed by ATR-FTIR and Raman spectroscopies, which revealed specific hydrogen bonding interactions between GEN, β-CD and the polymer chains, as well as changes in the PVA network structure induced by the encapsulated guest. The release kinetics of GEN from PVA-β-CD (with different β-CD contents) were analyzed using the Peppas-Sahlin model, which demonstrated that β-CD concentration acts as a tuning parameter controlling not only the overall release rate but also the underlying transport mechanism. The results presented in this study provide a molecular-level understanding of the supramolecular and mass-transport phenomena controlling the functional performance of this drug delivery system.