Abstract:We report here on ion-exchange polymeric nanoparticles from a linear copolymer of maleic anhydride methyl vinyl ether esterified with 30% octadecanol. The side chains for the polymer structure were optimized through metadynamics simulations, which revealed the use of octadecanol esters generates ideal free energy surfaces for drug encapsulation and release. Nanoparticles were synthesized using a solvent evaporation-precipitation method by mixing the polymer solution in acetone into water; upon acetone evaporation, a nanodispersion with an average particle size of ∼150 nm was obtained. Gentamicin sulfate, possessing five amino groups, was spontaneously entrapped in the nanocarrier by ionic interactions. Encapsulation efficiency increases significantly with the increase in pH and ionic strength. In vivo results demonstrate high gentamicin (GM) content in the enteric chamber (AUC 8207 ± 1334 ($μ$g min)/mL) compared to 3% GM solution (AUC 2024 ± 438 ($μ$g min)/mL). The formulation was also able to significantly extend the release of gentamicin when applied to rabbit cornea. These anionic nanoparticles can be used for extended-release of other cationic drugs.