Studio teorico di membrane bicompatibili per applicazioni farmaceutiche

To design advanced dosage forms, suitable carrier materials are used to overcome the undesirable properties of drug molecules. Hence various kinds of high-performance biomaterials are being constantly developed. From the viewpoint of the optimization of pharmacotherapy, drug release should be controlled in accordance with the therapeutic purpose and pharmacological properties of active substances. The main objective of the present thesis was to characterize the interactions between drugs and drug carriers by using combined molecular dynamics, molecular mechanics, and docking computational techniques. These simulations are likely to benefit the study of materials by increasing our understanding of their chemical and physical properties at a molecular level and by assisting us in the design of new materials and predicting their properties. Simulations are usually considerably cheaper and faster than experiments. Molecular simulations also offer a unique perspective on the molecular level processes controlling structural, physical, optical, chemical, mechanical, and transport properties. In particular the attention was put on cyclodextrinic carriers supported on membrane and molecularly imprinted polymers. Thus, structural information, such as the geometries of the cyclodextrinic complexes, and thermodynamic data, i.e. the variation of the enthalpy, were considered to draw a complete picture of the βCD-drug interactions. The results were in good agreement with the experimental data found in the measurement of stability constants. Finally the molecular dynamics on the polymeric system formed by adding on the surface of PEEK-WC the βCD-drug complex showed the release of the included drug in a water solution. The docking and molecular mechanics techniques provided also informations on the geometry and the energy of complexation of a β-cyclodextrin derivative with naringin showing that the driving force for the host-guest complexation is due to the van der Waals interaction. Moreover the molecular dynamics calculations provided details on the complexation of naringin on the PEEK-WC surface containing the β-cyclodextrin derivative. The binding affinity and selectivity of MIP towards drug template were calculated from the interaction energy between the ligand and the monomers and from docking simulations, respectively, as also the number of hydrogen bonds was determined. Our computational results shown a higher interaction energy between the drug template and monomers and justified the experimental data of selective recognition and rebinding of the template in terms of MIP performance confirming the reliability of our computational method. Moreover the diffusion coefficient of 5-FU into a PMAA matrix on the release step was determined.Thus, atomistic modelling of material structure was a tool for understanding the mechanisms of physical processes on atomic and molecular levels, gaining insights into the molecular origins of behaviour of bulk polymers.