Fine-tuning the release of molecular guests from mesoporous silicas by controlling the orientation and mobility of surface phenyl substituents

Manzano, J. Sebastián
Singappuli-Arachchige, Dilini
Parikh, Bosky L.
Slowing, Igor
Major Professor
Committee Member
Journal Title
Journal ISSN
Volume Title
Research Projects
Organizational Units
Organizational Unit
Ames Laboratory
Organizational Unit
Journal Issue
ChemistryAmes Laboratory
Phenyl-functionalized mesoporous silica materials were used to explore the effect of non-covalent interactions on the release of Ibuprofen into simulated body fluid. Variations in orientation and conformational mobility of the surface phenyl groups were introduced by selecting different structural precursors: 1) a rigid upright orientation was obtained using phenyl groups directly bound to surface Si atoms (Ph-MSN), 2) mobile groups were produced by using ethylene linkers to connect phenyl groups to the surface (PhEt-MSN), and 3) groups co-planar to the surface were obtained by synthesizing a phenylene-bridged periodic mesoporous organosilica (Ph-PMO). The Ibuprofen release profiles from these materials and non-functionalized mesoporous silica nanoparticles (MSN) were analyzed using an adsorption-diffusion model. The model provided kinetic and thermodynamic parameters that evidenced fundamental differences in drug-surface interactions between the materials. All phenyl-bearing materials show lower Ibuprofen initial release rates than bare MSN. The conformationally locked Ph-MSN and Ph-PMO have stronger interactions with the drug (negative ΔG of adsorption) than the flexible PhEt-MSN and bare MSN (positive ΔG of adsorption). These differences in strength of adsorption are consistent with differences between interaction geometries obtained from DFT calculations. B3LYP-D3-optimized models show that π-π interactions contribute more to drug adsorption than H-bonding with silanol groups. The results suggest that the type and geometry of interactions control the kinetics and extent of drug release, and should therefore serve as a guide to design new drug delivery systems with precise release behaviors customized to any desired target.
This is a manuscript of an article published as Manzano, J. Sebastián, Dilini Singappuli-Arachchige, Bosky L. Parikh, and Igor I. Slowing. "Fine-tuning the release of molecular guests from mesoporous silicas by controlling the orientation and mobility of surface phenyl substituents." Chemical Engineering Journal 340 (2018): 73-80. DOI: 10.1016/j.cej.2017.12.015. Copyright 2017 Elsevier B.V. Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0). Posted with permission.