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.