Ethoxylated copolymersurfactants for the HFA134a–water interface: interfacial activity, aggregate microstructure and biomolecule uptake

Abstract

In this work we examine the aggregation behavior of ethoxylated copolymer surfactants in 1,1,1,2-tetrafluoroethane in the presence of water, and the ability of such aggregates to uptake a model biomolecule. Our approach consists of developing a rational framework for understanding the behavior of interfacially active species at the HFA134a–water (HFA134a|W) interface using a combination of in situ high-pressure tensiometry, spectroscopy, and small-angle neutron scattering (SANS). The optimum hydrophilic-to-HFA-philic balance (HFB) for the ethylene oxide–propylene oxide–ethylene oxide (EO_nPO_∼43EO_n, where subscripts indicate the number of repeat units) surfactant series at the HFA134a|W interface was determined at 298 K and saturation pressure of the propellant (under pressure). The selection of promising candidates for the reverse aggregate formation studies was based on the tension vs. HFB scan. Tensiometric information revealed that EO₃PO₄₃EO₃ occupies a very large area per molecule at the HFA134a|W interface, which represents a general trend for compressible solvents that are small and also able to interact with water more favorably than alkane solvents. The water solubilization capacity of the EO₃PO₄₃EO₃surfactant was investigated in situ by UV-vis spectroscopy, with a suitable solvatochromic probe. At a surfactant concentration above the determined critical aggregation concentration, a shift in the absorption maximum of the probe towards that of pure water was observed as the water-to-surfactant ratio increases. A similar but more pronounced shift was observed in the presence of a co-solvent. The nature of the aqueous environment associated with the aggregates is discussed based on the spectroscopic results. The microstructure of the aggregates is investigated by SANS. Scattering curves were also used to confirm the uptake of a model protein in the reverse aggregates. The relevance of this work stems from the fact that reverse aggregates of water in HFA134a are potential candidate formulations for the delivery of hydrophilic drugs, including biomolecules, to and through the lungs.