Abstract
Polyurethanes are widely used in different industries, as insulators, coating or adhesive agents. Several of their medical applications include various implants, artificial heart valves, surgical instruments or catheters. The versatility and biocompatibility of these polymer products lead to their application as drug or genetic material delivery systems. We aim to evaluate different parameters that affect the encapsulation efficiency of polyurethanes, using a computational approach, in order to improve the transmembrane transfer and the bioavailability of an active agent loaded inside a drug delivery system. 2D structures of different etheric- and esteric-PU macromolecular chains were modeled in ChemBioDraw, while molecular structures of the three active agents (Deoxyribonucleic acid, Guanidine,1`-[(methylethanediylidene)dinitrilo]di-, mixt. with Calf Thymus DNA, and 2`-Deoxycytidine-5`-phosphonic acid) were imported from PubChem database. Open software such as Open Babel and PyRx were used to convert files and to analyze the binding affinity based on the predicted dissociation constants. Structural parameters of the tested compounds were calculated in HyperChem 8.0. The polymer chains showed very large values for van der Waals potentials, refractivity and polarizability compared to the active agents. Even if there were no major differences in terms of binding affinities between the tested assemblies, the best orientation ligand-macromolecule was the 2`-Deoxycytidine-5`-phosphonic acid encapsulated inside LDI and PEG-based polyurethane carrier. On the other hand, the values of Root Mean Square Deviation have identified that the best geometric fit to be the Deoxyribonucleic acid encapsulated inside IPDI and PCL-based polyurethane macromolecule. The assemblies between genetic materials and polyurethane drug delivery systems are not experimentally known and this study could orientate towards new potential therapies. These results indicate that there is no significant change in the values of the docking parameters with different PU synthesis precursors; however, a good compatibility between LDI and PEG-based chain and 2`-Deoxycytidine-5`-phosphonic acid was identified. Further studies are needed to evaluate the in vitro and in vivo utility of this finding.
Keywords: dissociation affinity; drug carrier; drug delivery; isocyanate; polymer; structure