Pulsatile Drug Delivery Based on a Complexation-Decomplexation Mechanism

Copolymer networks of poly(methacrylic acid) grafted with poly(ethylene glycol) exhibit pH-dependent swelling behavior due to the reversible formation/dissociation of interpolymer complexes. Because of the complexation/decomplexation phenomena, these gels exhibit large changes in their structure and are able to deliver drugs at varying rates depending on the pH of the environmental fluid. The effects of copolymer composition and the environmental pH on the network structure and the drug release characteristics were studied. The average network mesh was 3 times larger in gels swollen in neutral or basic media than in acidic solutions in which complexation occurred. The largest changes in network structure were observed in gels containing nearly equimolar amounts of methacrylic acid and ethylene glycol. Drug diffusion coefficients, determined through solute release experiments, varied by two-orders of magnitude between the uncomplexed and complexed states.