Molecular Dynamics Simulation and Experimental Validation of Novel Biodegradable Polymer Blends for Drug Delivery in Malaria Treatment

The rational design of biodegradable polymer drug delivery systems for antimalarial agents requires detailed molecular-level understanding of polymer-drug interactions, polymer chain dynamics, and degradation kinetics, which are inaccessible through experimental methods alone. This study employed molecular dynamics simulation coupled with experimental validation to develop novel biodegradable polymer blends for controlled-release delivery of artemisinin-based antimalarial drugs, with specific relevance to improving treatment adherence in Nigerian rural settings where daily dosing compliance is a challenge. Coarse-grained and all-atom molecular dynamics simulations were conducted for blends of polylactic acid, polyglycolic acid, polyhydroxybutyrate, and polycaprolactone at varying compositions to predict drug encapsulation efficiency, polymer miscibility, glass transition temperature, mechanical properties, and hydrolytic degradation rates at physiological temperature and pH. Flory-Huggins interaction parameters were calculated from simulation trajectories to guide blend composition optimisation. Five optimised blend compositions were synthesised by solvent casting and electrospinning, and artemisinin-loaded nanoparticles were prepared by nanoprecipitation. Experimental characterisation confirmed simulation-predicted miscibility behaviour, glass transition temperatures within 8 degrees Celsius of predicted values, and drug loading efficiencies within 5 percent of predicted encapsulation efficiencies. In vitro drug release profiles demonstrated tunable release kinetics from 4 to 21 days depending on blend composition, consistent with predicted degradation rates. The original computational-experimental integration framework developed provides a resource-efficient approach to biodegradable drug delivery system design applicable to other neglected tropical disease treatment challenges in Nigeria.

Keywords: molecular dynamics simulation, biodegradable polymers, drug delivery, artemisinin, malaria treatment