Composite alginate hydrogels: An innovative approach for the controlled release of hydrophobic drugs

We present an innovative methodology for the sustained delivery of hydrophobic drugs using composite hydrogels, prepared by embedding oil-in-water microemulsions in hydrophilic hydrogels. The hydrophobic nature of the microemulsion core enhances the solubilization of hydrophobic drugs, while the crosslinked matrix could be readily used as a solid controlled delivery vehicle. A microemulsion was formulated from pharmaceutical accepted components; the droplets diameter was shown to be about 10 nm by dynamic light scattering, cryo-transmission electron microscopy and small-angle X-ray scattering (SAXS). Combining the microemulsion with alginate solution and crosslinking with calcium ions resulted in a clear hydrogel. A model hydrophobic drug, Ketoprofen, precipitated from the alginate hydrogel, but the drug-containing composite hydrogel was clear and macroscopically homogeneous. The nanostructure was investigated by SAXS; scattering plots indicate that oil droplets exist in the composite hydrogel. Release profiles of the drug from the composite hydrogel with various concentrations of polymer and crosslinker demonstrate the applicability of this system as a controlled delivery vehicle, and suggest that the release rate is governed not by the microemulsion structure but, rather, by the network properties. Furthermore, it was demonstrated that the release rate could be tailored for a specific application utilizing different alginate and calcium concentrations. The generalization of the methodology of including hydrophobic drugs in composite gels is discussed.