Studio teorico di membrane bicompatibili per applicazioni farmaceutiche
To design advanced dosage forms, suitable carrier materials are used to\novercome the undesirable properties of drug molecules. Hence various\nkinds of high-performance biomaterials are being constantly developed.\nFrom the viewpoint of the optimization of pharmacotherapy, drug release should\nbe controlled in accordance with the therapeutic purpose and pharmacological\nproperties of active substances.\nThe main objective of the present thesis was to characterize the\ninteractions between drugs and drug carriers by using combined molecular\ndynamics, molecular mechanics, and docking computational techniques. These\nsimulations are likely to benefit the study of materials by increasing our\nunderstanding of their chemical and physical properties at a molecular level and\nby assisting us in the design of new materials and predicting their properties.\nSimulations are usually considerably cheaper and faster than experiments.\nMolecular simulations also offer a unique perspective on the molecular level\nprocesses controlling structural, physical, optical, chemical, mechanical, and\ntransport properties.\nIn particular the attention was put on cyclodextrinic carriers supported on\nmembrane and molecularly imprinted polymers.\nThus, structural information, such as the geometries of the cyclodextrinic\ncomplexes, and thermodynamic data, i.e. the variation of the enthalpy, were\nconsidered to draw a complete picture of the βCD-drug interactions. The results\nwere in good agreement with the experimental data found in the measurement of\nstability constants. Finally the molecular dynamics on the polymeric system\nformed by adding on the surface of PEEK-WC the βCD-drug complex showed the\nrelease of the included drug in a water solution.\nThe docking and molecular mechanics techniques provided also\ninformations on the geometry and the energy of complexation of a β-cyclodextrin\nderivative with naringin showing that the driving force for the host-guest\ncomplexation is due to the van der Waals interaction. Moreover the molecular\ndynamics calculations provided details on the complexation of naringin on the\nPEEK-WC surface containing the β-cyclodextrin derivative.\nThe binding affinity and selectivity of MIP towards drug template were\ncalculated from the interaction energy between the ligand and the monomers and\nfrom docking simulations, respectively, as also the number of hydrogen bonds\nwas determined. Our computational results shown a higher interaction energy\nbetween the drug template and monomers and justified the experimental data of\nselective recognition and rebinding of the template in terms of MIP performance\nconfirming the reliability of our computational method. Moreover the diffusion\ncoefficient 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\nmechanisms of physical processes on atomic and molecular levels, gaining\ninsights into the molecular origins of behaviour of bulk polymers.