Semi-interpenetrating network (IPN) of sodium alginate (NaAlg) and N-isopropylacrylamide (NIPAAm) microspheres were prepared by water-in-oil (w/o) emulsification method. The microspheres were encapsulated with 5-fluorouracil (5-FU) and release patterns carried in 7.4 pH at temperatures of 25 and 37 degrees C. The semi-IPN microspheres were characterized by Fourier transform infrared spectroscopy (FTIR). Differential scanning calorimetry (DSC) and scanning electron microscopic studies were done on the drug-loaded microspheres to confirm the polymorphism of 5-FU and surface morphology of microspheres. These results indicated the molecular level dispersion of 5-FU in the semi-IPN microspheres. Particle size and size distribution were studied by laser light diffraction technique. Microspheres exhibited release of 5-FU up to 12 h. The swelling studies were carried in 1.2 and 7.4 pH buffer media at 25 and 37 degrees C. Drug release from NaAlg-NIPAAm semi-IPN microspheres at 25 and 37 degrees C confirmed the thermosensitive nature by in vitro dissolution. The micro domains have released in a controlled manner due the presence of NIPAAm in the matrix. (c) 2007 Wiley Periodicals, Inc.