title: A calorimetric investigation of doxorubicin-polymer bead interactions.
abstract: Isothermal titration calorimetry (ITC) was utilised to investigate suitability of the technique to determine the stoichiometry and thermodynamics of the interactions that occur between a commonly used chemotherapeutic drug, namely doxorubicin, and a polymer bead-based drug delivery embolisation system (DC Bead™). Six temperatures were selected for drug-polymer titrations (293-313 K) and in all cases an initially exothermic signal reverted to an endothermic response upon the saturation of the beads with drug. From these experiments, and subsequent calculations, the molar ratio of drug to SO3(-) (polymer) was found to be 0.4:1 at all temperatures studied. Enthalpic data was calculated from the raw ITC data with an average enthalpy of drug-polymer binding of - 14.8 kJ mol(-1) at 293 K through to - 19.4 kJ mol(-1) at 313 K implying the process is enthalpically-driven yet only affected by an increase in experimental temperature to a limited extent whereby an increase in experimental temperature results in a small increase in the negativity in change in enthalpy recorded. The application of ITC in this study (with its unique ability to monitor real-time interactions and facilitate stoichiometric calculations) resolves the lack of knowledge regarding the thermodynamics of this specific drug-polymer interaction. This study confirms that ITC is not only useful for this specific system, but also highlights the potential use of ITC for more general studies in this area.
authors.affiliation: Department of Pharmacy, School of Applied Science, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK. Electronic address: l.waters@hud.ac.uk.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Waters
authors.affiliation: Department of Pharmacy, School of Applied Science, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK; Biocompatibles UK Ltd., a BTG International group company, Lakeview, Riverside Way, Watchmoor Park, Camberley, Surrey GU15 3YL, UK.
authors.forename: Tanya S
authors.initials: TS
authors.lastname: Swaine
authors.affiliation: Biocompatibles UK Ltd., a BTG International group company, Lakeview, Riverside Way, Watchmoor Park, Camberley, Surrey GU15 3YL, UK.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000476:Alkanesulfonates / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002151:Calorimetry / Q000379:methods*; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D008863:Microspheres; D010316:Particle Size; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000178:Acrylamides; D000476:Alkanesulfonates; D000970:Antineoplastic Agents; C056288:2-acrylamido-2-methylpropanesulfonate; D004317:Doxorubicin; D011142:Polyvinyl Alcohol
keywords: Binding; DC Bead™; Doxorubicin; ITC; Polymer; Thermodynamics