title: Cross-linked Pluronic-g-Polyacrylic acid microgel system for the controlled release of doxorubicin in pharmaceutical formulations.
abstract: The binding of doxorubicin (DOX) to cross-linked Pluronic F127-g-PAA-EGDMA and L92-g-PAA-EGDMA microgels at different alpha (α) and salt concentrations was investigated using isothermal titration calorimetric (ITC), optical and scanning electron microscopic techniques (SEM). We seek to elucidate the mechanisms of interaction and the release of DOX from cross-linked microgels composed of Pluronic and poly(acrylic acid). The ITC results indicated a high binding affinity of DOX to the microgel, which is a function of salt concentrations due to the impact of electrostatic shielding on the DOX-binding process. Applying the polyelectrolyte theory allows the decoupling of the Gibbs free energy of binding that describes the role of non-electrostatic interaction of DOX and the microgel. The presence of DOX within the microgel resulted in the collapse of the microgel due to charge shielding, π-π interactions and self-association of polymer-bound DOX molecules. The diffusion of DOX through the microgel is controlled by the dissociation of COO-/DOX+coupling pairs.
authors.affiliation: Singapore-MIT Alliance, Singapore; School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore.
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Chemical Engineering and Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Grishkewich
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: L
authors.initials: L
authors.lastname: Bromberg
authors.affiliation: Singapore-MIT Alliance, Singapore; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: T Alan
authors.initials: TA
authors.lastname: Hatton
authors.affiliation: Department of Chemical Engineering and Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada. Electronic address: mkctam@uwaterloo.ca.
authors.forename: Kam C
authors.initials: KC
authors.lastname: Tam
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients; D005782:Gels; D010316:Particle Size
chemical_list: D000179:Acrylates; D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; C000615932:Pluronic-poly(acrylic acid); D004317:Doxorubicin
keywords: Binding; Doxorubicin; Drug release; Microgels; Pluronic-g-Polyacrylic acid; Thermodynamics