241: Modeling doxorubicin partitioning between polyelectrolyte complexes

Abstract: Polyelectrolyte complexes (PEC) are a unique class of materials resulting from the spontaneous phase separation of oppositely charged polymers mixed within an aqueous solution. PECs can be used as effective drug carriers, protecting it from early degradation and facilitating its controlled release. Despite their use, much still remains unknown regarding the influence of PEC sequencing on drug uptake and encapsulation efficiency. Addressing this issue, we use molecular dynamics simulations, with the Martini 3.0 force field, to model the partitioning behavior of doxorubicin for six hydrophobically patterned PEC systems made from highly charged peptide oligomers. These systems were previously characterized experimentally by Tabendeh et al. and were found to showcase preferential encapsulation of doxorubicin based on their hydrophobicity. Here, we employ slab simulation geometries and free energy methods to recapture the observed trends in doxorubicin partitioning. By recapturing these trends using a coarse grained model, we can derive further insight into how peptide-doxorubicin interactions facilitate the observed partitioning behavior, guiding the development of PEC-based drug delivery methods.