• ethyl butyrate
• methacrylate triblock copolymer
• nanodetoxification
• nonionic surfactants
• o/w microemulsions
• Pluronic F127
• ternary phase diagram

Only recently oil-in-water microemulsions have gained considerable interest as parenteral detoxifying agents which are thought to circulate through the bloodstream and capture toxins by adsorption of the toxin to the surface of microemulsions colloidal particles or internalization (partition) of the toxic compound within them.
For a given microemulsion system, relative concentration of the components and environmental conditions are the two most important factors determining its final properties, reflecting directly on their ultimate drug uptake efficiency. In fact, the dynamics, size, and morphology of their nanodomains completely rely on these two variables, and the best way to establish a relationship between them is by the construction of a proper phase diagram. Although time consuming, the construction of a phase diagram is the only way to avoid the production of metastable systems and permit one to choose the optimal formulations of a multi-component system for a specific application.
The aim of this study was to investigate the formation of oil-in-water microemulsions stabilized by two nonionic block copolymers, Pluronic F127 and a novel synthesized ABC PEG- and alkyl methacrylate- based triblock copolymer, currently denoted as P16 and for which a Patent Application has been processed, containing the pharmaceutically acceptable oil, ethyl butyrate, and phosphate buffered saline as aqueous phase. For each ternary system the concentration range of components resulting in oil-in-water microemulsions with droplet size smaller than 100 nm was determined by the construction of an isothermal (25° C) phase diagram.
Both ternary phase diagrams were constructed using the so-called oil titration method and the phase behavior and nanostructure of samples, over a wide range of relative compositions, was followed through visual observation, optical polarized microscopy and dynamic light scattering (DLS). However, for the P16-based ternary system the morphology of the nanodomains of one of the samples classified as oil-in-water microemulsion was directly imaged using Transmission electron microscopy (TEM). TEM photomicrographs revealed a core-shell structure of the microemulsion, confirming the results and hypotheses drawn on the basis of DLS experiments, which in general only provide indirect evidence of microstructures. Moreover, the more viscous samples were characterized by rheological measurements showing non-Newtonian, plastic or pseudo-plastic behavior.
The self-aggregation properties of the newly synthesized polymer and its ability to micro-emulsify the selected oil phase was directly compared to Pluronic F127. Moreover, resulting oil-in-water microemulsions from the two ternary systems were evaluated on the basis of homogeneity and droplet size, outlining the advantages of using one surfactant over the other for the development of microemulsions intended to be used as detoxifying agents.
The results showed that P16 forms o/w microemulsions in a wider range of relative concentration of components as compared to Pluronic F127 and that the solubilization of ethyl butyrate is improved more than twice when using the former as surfactant at a copolymer concentration range of 12-18% (w/w). The difference in the average droplet size between the two ternary systems was not significant (~ 25 nm for Pluronic F127-based formulations and ~ 30 nm for P16-based formulations) but polydispersity was minimum in the case of P16-stabilized o/w microemulsions, suggesting a more uniform globule size distribution and a higher stability.
The findings reported here are therefore relevant for the design and development of fine and homogeneous microemulsions stabilized by the newly synthesized polymer P16 which, although can be used for diverse applications, their potential as drug scavenger is particularly emphasized.