Understanding the self-assembly of the polymeric drug solubilizer Soluplus

Hypothesis: Soluplus (R) is one of the most widely used amphiphilic copolymers in drug delivery and has been reported to strongly enhance the adsorption of model drugs. However, there is still a limited understanding of its micellar behavior as it responds to the different routes of administration, which involve important changes in concentration. Experiments: The microstructure of Soluplus aqueous solutions has been investigated at a wide range of polymer concentrations (2 x 10(-6) - 0.2 g/mL) by a combination of diffusion NMR (dNMR), small angle X-ray scattering (SAXS), static (SLS) dynamic (DLS) light scattering and viscosity measurements. These techniques have been coupled with surface tension measurements to frame the polymer's critical micellar concentration (cmc). Findings: We demonstrate the presence at all tested concentrations of two forms of Soluplus, with hydrodynamic radii of 3 and 26 nm, where the fraction of smaller objects accounts for as much as 60-70%. dNMR, SAXS, DLS and SLS indicate that Soluplus spontaneously self-assembles into large spherical particles with a core-shell structure. However, self-assembly takes place three orders of magnitude above the cmc evaluated via surface tension measurements. Instead of the traditional cooperative micellization process, we propose a thermal-activated isodesmic self-assembly of the small aggregates into core-shell micelles. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

This study investigates the microstructure and micellization process of Soluplus at different concentrations. The results show the presence of two forms of micelles at all concentrations, and the micellization occurs at much higher concentrations than the critical micellar concentration. The micellization process is suggested to be thermally activated isodesmic self-assembly.