Effect of PEG conformation and particle size on the cellular uptake efficiency of nanoparticles with the HepG2 cells

Core-shell nanoparticles were prepared from di-block copolymer of methoxy poly(ethylene glycol)-polycaprolactone (MePEG-PCL) and tri-block copolymer of polycaprolactone-poly(ethylene glycol)-polycaprolactone (PCL-PEG-PCL). The MePEG-PCL copolymers form nanoparticles with PEG "brush" on their surfaces and PCL-PEG-PCL copolymers form nanoparticles with a "mushroom-like" structure on their surfaces in aqueous solution. The morphology and size of nanoparticles were measured by field emission scanning electron microscopy (FESEM) and laser light scattering (LLS). All the nanoparticles are in spherical shape and the sizes are less than 200 nm. The sizes of the nanoparticles increases with increasing PCL segment length. The drug-loading content results showed that the optimal feeding ratio of paclitaxel to copolymer is dependent upon the copolymer composition and 5% is a suitable feeding ratio. The in vitro release behavior exhibits a sustained release manner and is affected by copolymer composition. Experimental results showed that cells would prefer to attach to more hydrophobic polymers. Comparing between MePEG-PCL and PCL-PEG-PCL of similar hydrophobicity, more HepG2 cells have attached to the MePEG-PCL copolymer films because a denser PEG layer was formed on the surfaces of PCL-PEG-PCL copolymers. In vitro cellular uptake experimental results indicated that HepG2 cells prefer smaller nanoparticles with the same PEG configuration on their surfaces. The cytotoxicity of paclitaxel-loaded nanoparticles seemed to increase with increasing drug loading of nanoparticles against HepG2 cells.