The intermolecular interactions between the model protein, bovine serum albumin (BSA) and a biocompatible polysaccharicle, sodium alginate, have been investigated. Both the native BSA and the heat pre-denatured BSA were utilized to study, in parallel, the effect of protein conformational change during the protein-alginate complex formation. In this work, a comparison was performed between the native BSA and the heat-denatured BSA incubated sodium alginate mixtures by using zeta potential analyzer, dynamic light scattering (DLS) and turbidimetric analysis of the systems in combination with protein conformational tools, Fourier transform infrared spectroscopy (FT-IR) and size exclusion chromatography (SE-HPLC). The experimental results demonstrate that the intermolecular chain associations were formed between alginate chains and protein molecules in either the native form or the heat pre-denatured form, mainly driven by the electrostatic interactions between the oppositely charged amino acids and the anionic polysaccharide macromolecules. However, the majority of BSA was recovered from the dissociation of protein-alginate complexes and maintained its secondary structure and conformational property. Therefore, alginate is promising as a bioactive compound carrier. (c) 2008 Elsevier Inc. All rights reserved.