PEGylated nanocapsules of perfluorooctyl bromide: Mechanism of formation, influence of polymer concentration on morphology and mechanical properties.

PEGylated nanocapsules containing a liquid core of perfluorooctyl bromide (PFOB) were formulated by an emulsion-evaporation process to be further used as ultrasound contrast agents (UCAs). In an attempt to modulate their acoustic response, related to their shell thickness-to-radius ratio, the initial concentration of polymer was varied in the formulation. Indeed, thinner shells may lead to higher echogenicity. PEGylated nanocapsules morphology was studied by electron microscopy, Small Angle Neutron Scattering and (19)F NMR spectroscopy and related to their mechanical properties to allow a better understanding of their mechanism of formation. We show that the variation of polymer concentration in the formulation impacts the formation mechanism of nanocapsules, and consequently their morphology and mechanical properties. Using low concentration of Poly(ethylene glycol)-b-poly(dl-lactide-co-glycolide) (PLGA-b-PEG), it is impossible to reduce the shell thickness of the UCA, most probably due to dewetting of the polymer layer at the PFOB/water interface. This leads to the coexistence of thick shells along with free PFOB droplets. On the other hand, for high polymer concentration, PEGylated nanocapsules with thick shells were produced with high encapsulation efficiency.