Block copolymer surface coverage on nanoparticles

Surface modification plays an important role in making nanoparticle (NP) formulations a viable route for drug delivery. Steric stabilizing layers are required for particle stability in vitro and to prolong circulation in vivo. To best tailor such formulations, understanding and control of surface coverage is necessary. In this study, surface coverage of nanoparticles prepared by Flash NanoPrecipitation, a block copolymer-directed rapid precipitation technique using a multi-inlet vortex mixer, is analyzed. Monodisperse polystyrene nanoparticles of 210 and 560 nm are used as model NPs to explore the effect of polymer concentration on polystyrene-block–polyethylene glycol attachment during nanoparticle preparation. Dynamic light scattering (DLS) in conjunction with a quantitative colorimetric iodine assay for polyethylene glycol concentration is employed to analyze surface coverage. For polymer concentrations above 0.53 wt.% a distinct population of free micelles is observed along with the coated NPs. The block copolymer coating has a thickness of ∼25 nm as observed by DLS. The coated NPs are isolated from free micelles by centrifugation and the concentration on the NP surface is quantified. The 3K PEG blocks (PS-b–PEG, 1.5K-b-3K) occupy a surface area of 9.29 nm2/polymer, which is closer packed than the Flory size of the 3K PEG which would be 13.6 nm2/polymer, and less dense than would be expected for a fully equilibrated chain, 0.75 nm2/polymer.