Complexation and release of doxorubicin from its complexes with pluronic P85-b-poly(acrylic acid) block copolymers

Poly(acrylic acid) (PAA) was attached on both termini of Pluronic P85 copolymer (EO27PO39EO27) via atom transfer radical polymerization (ATRP) to produce a novel block copolymer, PAA-b-P85-b-PAA (P85PAA). The P85PAA-DOX complex formation and drug loading were strongly dependent on the PAA segment length and pH, where the protonation of carboxyl groups in the PAA segment at pH < 7.2 reduced the binding sites of DOX onto P85PAA chains, resulting in a diminished DOX uptake at low pH. The composition of copolymer-DOX complexes at pH 7.2 was close to the stoichiometric 1:1 DOX:carboxyl molar ratio, confirming the dominance of electrostatic interactions between cationic DOX molecules and carboxyl groups. The stability study of the copolymer-DOX complex suggested that non-polyelectrolyte interactions may also participate in the complexation of drug and P85PAA block copolymer. DOX loading at pH 5.0 decreased to 60% of the total binding capacity, indicating that protonation of carboxyl groups reduced the DOX binding to P85PAA block copolymer. DOX release from the complex is a pH-responsive process, where the protonation of carboxyl groups at mildly acidic condition resulted in a faster dissociation of copolymer-DOX complex, leading to an accelerated release of DOX at pH 5.0. Thus, complexation of DOX with P85PAA yielded a drug delivery system affording a pH-triggered release of DOX in an acidic environment of pH 5.0. (C) 2007 Elsevier B.V All rights reserved.