Bioinspired polymer nanoparticles omit biophysical interactions with natural lung surfactant

Herein, we report the attenuated impact of bioinspired nanoparticles on the essential function of lung surfactant. Colloidal particles made from poly(lactide) caused a significant loss of surfactant protein B (and C) from a natural lung surfactant accompanied by a decline in surface activity under static conditions and surface area cycling. No such perturbation of lung surfactant composition and function was observed for polymer nanoparticles coated with bioinspired poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC). More specifically, increasing the PMPC-coating layer thickness (≥3 nm) and density (dense conformation, distance of individual polymer chains of ≤3 nm) on the polymer nanoparticle surface diminished bioadverse events. PMPC-coated poly(lactide) nanoparticles provoked a less severe perturbation of the utilized lung surfactant when compared to colloidal counterparts coated with poly(ethylene glycol). Overall, a steric shielding of colloidal drug delivery vehicles with bioinspired PMPC can be considered as a valuable approach for the rationale development of biocompatible nanomedicines intended for lung delivery.