“Smart” alginate–hydroxypropylcellulose microbeads for controlled release of heparin

“Smart” (thermosensitive) alginate–hydroxypropylcellulose (Alg/HPC) microbeads for controlled release of heparin were synthesized and the release profiles at various temperatures and for various alginate/HPC compositions were measured. Microbeads of regular spherical shape (ca. 3 μm in diameter) containing efficiently encapsulated heparin were obtained using an emulsification method. The internal structure of the bead was estimated by fluorescence microscopy using dansyl alginate as a labelled component. The microbeads surface structure and morphology were imaged in a dry state using scanning electron microscopy (SEM) and in water using atomic force microscopy (AFM). The microbead surface was shown to be covered by the regular network of pores with a mesh of ca. 30–60 nm. Lower critical solution temperature (LCST) of the Alg/HPC systems was measured spectrophotometrically (cloud point measurements). Heparin release profiles were obtained based on spectrophotometric detection of heparin complex with Azure A. Three-stage sustained release for at least 16 days was observed at 37 °C. This was correlated with the size of the pores present at the surface of microbeads. The release profile can be controlled by the temperature and composition of the Alg/HPC microbeads.