Acidity constant and DFT-based modelling of pH-responsive alendronate loading and releasing on propylamine-modified silica surface

A computational methodology that couples the acidity (Ka) and density functional theory (DFT) calculations has been developed to explain the pH-dependent drug loading on and releasing from mesoporous silica nanoparticles. The model has been validated by investigating the pH-dependent loading and releasing of a bisphosphonate drug molecule, alendronate, on a propylamine-modified quartz surface (101), a model for functionalized mesoporous silica nanoparticles. The pH-dependent interacting molecular species are the neutral and anionic forms of the drug molecule, silanol group of quartz surface and the functional group in the case of functionalized quartz surface. The interaction energies of all the molecular species of alendronate with silica surface are calculated by using the DFT-based CASTEP method. Five molecular states of alendronate (D0, D−, D2−, D3− and D4−), two for silica surface (S0 and S−) and two for propylamine (P+ and P0) are considered. Ten possible combinations of interactions of alendronate with silica surface and twenty for alendronate and propylamine-functionalized silica surfaces are calculated. The relative probability of interaction of a particular pair of drug and surface combination at a particular pH is weighed by the product of their fractions, the latter is calculated by using the Handerson–Hasselbach equation. The total interaction energies at a particular pH are calculated by summing the possible individual interaction energies. The variation of total interaction energy with pH shows that the functional group of propylamine lowers the interaction energy at lower pH values (1–5), thus favouring adsorption or loading of the drug and increases the interaction energy at higher pH values (pH > 8) and thus favours desorption or release of the drug. This is in agreement with experimental results where it is shown that propylamine-functionalized mesoporous silica nanoparticles load alendronate in the pH range of 1–5 and release at pH = 8. This method can be used to predict the pH-dependent drug loading and releasing of a particular combination of drug and on a particular drug delivery system.