Polyelectrolyte-surfactant-complex nanoparticles as a delivery platform for poorly soluble drugs: A case study of ibuprofen loaded cetylpyridinium-alginate system

Previously, we reported on the surfactant cetylpyridinium chloride (CPC) as a crosslinker of alginate for the formation of stable polyelectrolyte-surfactant-complex nanoparticles. Here, we evaluate this system for increased solubility of a poorly soluble drug. The aim was to use CPC for solubilisation of ibuprofen and to use the micellar associates formed for alginate complexation and nanoparticle formation. We acquired deeper insights into the entropy led interactions between alginate, CPC and ibuprofen. Stable nanoparticles were formed across limited surfactant-to-polyelectrolyte molar ratios, with similar to 150 nm hydrodynamic diameter, monodispersed distribution, and negative zeta potential (-40 mV), with 34% ibuprofen loading. Their structure was obtained using small-angle X-ray scattering, which indicated disordered micellar associates when ibuprofen was incorporated. This resulted in nanoparticles with a complex nanostructured composition, as shown by transmission electron microscopy. Drug release from ibuprofen-cetylpyridinium-alginate nanoparticles was not hindered by alginate, and was similar to the release kinetics from ibuprofen-CPC solubilisates. These innovative carriers developed as polyelectrolyte-surfactant complexes can be used for solubilisation of poorly soluble drugs, where the surfactant simultaneously increases the solubility of the drug at concentrations below its critical micellar concentration and crosslinks the polyelectrolyte to form nanoparticles.