Interaction of surfactant and protein at the O/W interface and its effect on colloidal and biological properties of polymeric nanocarriers.

Graphical abstract Highlights • Interfacial and colloidal properties underlying synthesis of NPs by W/O/W technique. • Surfactant (F68) added from water improves colloidal and biological NP properties. • An in vitro model to mimic the first step of the W/O/W NP synthesis is developed • F68 added from water displaces more protein from interface protecting its structure. Abstract Hypothesis The use of polymer-based surfactants in the double-emulsion (water/oil/water, W/O/W) solvent-evaporation technique is becoming a widespread strategy for preparing biocompatible and biodegradable polymeric nanoparticles (NPs) loaded with biomolecules of interest in biomedicine, or biotechnology. This approach enhances the stability of the NPs, reduces their size and recognition by the mononuclear phagocytic system, and protects the encapsulated biomolecule against losing biological activity. Different protocols to add the surfactant during the synthesis lead to different NP colloidal properties and biological activity. Experiments We develop an in vitro model to mimic the first step of the W/O/W NP synthesis method, which enables us to analyze the surfactant-biomolecule interaction at the O/W interface. We compare the interfacial properties when the surfactant is added from the aqueous or the organic phase, and the effect of pH of the biomolecule solution. We work with a widely used biocompatible surfactant (Pluronic F68), and lysozyme, reported as a protein model. Findings The surfactant, when added from the water phase, displaces the protein from the interface, hence protecting the biomolecule. This could explain the improved colloidal stability of NPs, and the higher biological activity of the lysozyme released from nanoparticles found with the counterpart preparation. [ABSTRACT FROM AUTHOR]