"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 microm 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 degrees 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.