Polymeric Nanoparticles Engineered for Optimal Drug Delivery Using Atomistic Computational Simulation

Amphiphilic molecules can self-assemble into a wide range of morphologies, making them a promising candidate for drug delivery. Poly(lactic-co-glycolic acid)–poly(ethylene glycol) methyl ether (PLGA-MPEG), which is an amphiphilic copolymer, is a broadly used biodegradable drug carrier for drug delivery systems. In this study, computational molecular dynamics (MD) simulations were used to tailor polymeric nanoparticles with improved drug delivery efficacy. To optimize drug loading, customized copolymers with varying lactic acid to glycolic acid ratios, as well as the length of the MPEG chain, were considered. These simulations were carried out with varying amounts of the drug and copolymers. Our findings suggest the optimized conditions under which gemcitabine (GEM) was efficiently encapsulated in polymeric nanoparticles. The simulations reveal that varying the proportions of lactic and glycolic acid and MPEG chain lengths in copolymers can improve drug encapsulation efficiency. Increasing the glycolic content of the copolymers resulted in better GEM encapsulation, which corresponded to a higher binding energy. The strong interaction energy between GEM and the glycolic acid-rich copolymer suggested that the drug might have a slow-release profile. GEM and PLGGA-MPEGn have a higher average number of hydrogen bonds than that with PLGA-MPEGn and PLLGA-MPEGn. This indicates that the copolymer's flexibility increased as the concentration of glycolic acid in the copolymer increased, promoting the better formation of polymeric nanoparticles. This study has the potential to pave the way for the fabrication of polymeric nanocarriers capable of efficiently encapsulating drugs.