Synthesis and characterization of nanoemulsion-mediated core crosslinked nanoparticles, and in vivo pharmacokinetics depending on the structural characteristics.

Abstract For designing nanoparticles as drug carriers, a covalently crosslinked structure is necessary for the structural stability in vivo. In this study, we prepared core crosslinked nanoparticles through the formation of nanoemulsions stabilized by poly(ethylene glycol) (PEG)-bearing surfactants. The structural characteristics of these particles were carefully evaluated using small-angle scattering techniques including dynamic, static, X-ray, and neutron scattering. The particles demonstrated high stability even in vivo, with the suppression of premature drug release owing to the crosslinked structure. Interestingly, the ability to retain encapsulated molecules was dependent on the molecular weight of PEG in vivo, presumably due to the difference in the crowding density of PEG chains at the outermost surface. This suggests that conferring structural stability via a core crosslinked structure is surely important, but we also need to consider controlling the crowding density of the hydrophilic polymer chains in the particle shell when designing drug carriers.