Interaction of a biodegradable anionic polyphosphazene, poly[di(carboxylatophenoxy)phosphazene] (PCPP), with a model globular protein, hen egg white lysozyme, was investigated under near physiological conditions by means of turbidimetry, high-sensitivity differential scanning and isothermal titration calorimetry (ITC). The formation of soluble (non-stoichiometric) and insoluble (stoichiometric) interpolyelectrolyte complexes was demonstrated upon changes in the reaction mixture composition. The denaturation parameters of the bound lysozyme in the stoichiometric and non-stoichiometric complexes were determined. They point to a substantial decrease in conformational stability of the bound protein in the stoichiometric complex. In the non-stoichiometric complexes corresponding to a loose protein loading on the PCPP matrix an additional decrease in conformational stability of lysozyme was observed. It indicates unfolding of the protein at room temperature. ITC experiments were carried out at different temperatures in two modes: direct and reversible titrations. The direct titration curves were well approximated by the McGhee-von Hippel model that resulted in determination of the binding constant (similar to 1 x 10(6) M-1), apparent ligand size (similar to 10), cooperativity parameter (similar to 11) as well as the enthalpies of binding and ligand-ligand interaction. The heat capacity increments associated with the binding of the protein ligands and contact interaction between the bound ligands were comparable by value but opposite in sign. We discuss this effect in terms of changes in polar and apolar accessible surface areas of the bound protein ligands caused by the ligand-matrix and ligand-ligand interactions. (C) 2016 Elsevier Ltd. All rights reserved.