A molecular dynamics simulation study on the mechanism of loading of gemcitabine and camptothecin in poly lactic-co-glycolic acid as a nano drug delivery system

Abstract

The poly lactic-co-glycolic acid copolymer has become one of the most widely used synthetic macromolecules available for use in nanoscale drug delivery studies because of its biocompatibility and biodegradability. In this study, using computational molecular dynamics methods, combinations of polymer with different amounts of lactic and glycolic acid were compared for loading hydrophilic and hydrophobic of Gemcitabine and Camptothecin. These simulations were carried out in different ratios of the drug to the polymer. The results show that in all monomeric ratios, the amount of Camptothecin loading is higher, but on the other hand, the energy of the interaction of Gemcitabine with copolymer is greater, which can reduce its release rate from the system. By increasing the amount of glycolic acid in its system, it's the flexibility is increased and the formation of nanoparticles is also increased. Increasing the formation of nanoparticles leads to increase of the amount of drug loading of Gemcitabine. Conversely, with the increase in lactic acid content, the polymer's flexibility is diminished due to methyl group steric hindrance and the formation of nanoparticles is impaired. The results also show that for the formation of polymersomes, the drugs are first attached to the polymers, and then these compounds form the final nanoparticles as close as possible. Finally, this study suggests that poly lactic-co-glycolic acid is more suitable for loading hydrophobic drugs in any ratio of monomers. However, with increasing glycolic acid levels, its ability to load hydrophilic drugs also reaches a reasonable level.