Structural analysis of clay minerals intercalated with drugs solved by classical molecular dynamics and DFT methods

M. Pšenička¹, J. Škoda¹, M. Pospíšil¹, E. Gianni²

¹Charles University, Faculty of Mathematics and Physics, Prague 2, 12116, Prague, Czech Republic.

²Department of Geology, University of Patras, Rio, 26504, Patras, Greece

milan.psenicka@matfyz.cz

We report comparison of results of computational approach to physico-chemical description of clay minerals-based drug nanocarriers. Two different types of layered clay structures were described. The first one was Mg₂Al layered double hydroxide (LDH) intercalated with three drugs – mefenamic acid, sulindac and pravastatin. These drugs have anti-inflammatory and ant nociceptive effects (anti conduction of painful stimuli) and clay drug nanocarrier promotes its stability and sustained release process. The series of models with different amount and initial arrangement of intercalated drug were built and analysed in order to compare the calculation results with experimental data published in [1-3]. The second clay mineral was Halloysite intercalated with irinotecan drug. This mineral posses spiral shape nanotube morphology with different charge distribution on inner and outer surfaces. The results for different pH conditions will be presented [4].

DFT calculations for small crystal cell were carried out in QuantumEspresso using PBE exchange-correlation functional and MD calculations in Materials Studio software package using combination of two compatible forcefields CVFF and ClayFF. Comparison of calculated XRD patterns, basal spacings, concentration profiles, free volumes and mean square displacements will be presented for LDH supercell with total surface area of 400 Å2. DFT calculation were used for studying of interactions between LDH surface and drug. The whole complex structure was analysed by MD calculation on ns time scale. Results for modified forcefields in comparison with DFT substructure calculation and experimental results will be presented.

The energetically preferred bilayer or pseudo bilayer arrangement of intercalated drugs will be discussed in order to describe differences in behaviour for individual drugs and its impact on sustained release process.

Figure 1. Preferred bilayer arrangement of Pravastatin anions in the interlayer space of LDH

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4. E. Gianni, K. Avgoustakis, M. Pšenička, M. Pospíšil, D. Papoulis, Journal of Drug Delivery Science and Technology, (2019) – accepted (01.05.2019).