Characterisation of PEGylated PLGA nanoparticles comparing the nanoparticle bulk to the particle surface using UV/vis spectroscopy, SEC, ¹H NMR spectroscopy, and X-ray photoelectron spectroscopy

Graphical abstract: - Highlights: • We compared nanoparticles prepared on the basis of PLGA and PEG–PLGA for their polymeric composition in the particle bulk and on the surface. • We validated three analytical methods (UV/vis, SEC, ¹H NMR) for quantification of the polymeric stabiliser PVA and ¹H NMR for the quantification of PEG. • In the case of PEG–PLGA as starting material we observed significant PEG contents not only on the surface but even in the particle bulk. • We observed an unexpected accumulation of the polymeric stabiliser PVA on PEGylated particle surfaces. - Abstract: Hypothesis: The bulk and the surface structure of nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) and PLGA–PEG copolymer is expected to consist of different polymer compositions. An enrichment of hydrophilic PEG on the surface in combination with an accumulation of PLGA in the bulk is anticipated. Hence, the imbalance between bulk and surface composition should be detectable by suitable analytical methods. Experiments: Nanoparticles were assembled using an emulsion-evaporation method with polyvinyl alcohol (PVA) as stabiliser. Mixtures of PLGA and PLGA–PEG copolymer were applied to achieve variably PEGylated nanoparticles. The nanoparticle composition was analysed with respect to PLGA, PVA and PEG, comparing the polymer content of the nanoparticle bulk to the surface. For the bulk, PVA was quantified by a UV/vis spectroscopic method as well as size exclusion chromatography (SEC), and ¹H nuclear magnetic resonance (NMR) spectroscopy. PEG determination of the bulk was carried out using quantitative ¹H NMR spectroscopy. Surface composition was investigated by X-ray photoelectron spectroscopy (XPS). Findings: For the characterisation of the polymer composition ¹H NMR, SEC, and XPS-methods were successfully established and validated. Unexpectedly, a significant PEG content was detected within the particle bulk. The comparison of nanoparticle bulk to surface showed a surface accumulation of hydrophilic PVA with increasing PEGylation