Macromolecules, Vol.37, No.19, 7174-7180, 2004
Synthesis and characterization of PEG-based ether-anhydride terpolymers: Novel polymers for controlled drug delivery
A series of biodegradable poly(ether-anhydrides) composed of poly(ethylene glycol) (PEG), sebacic acid (SA), and 1,3-bis(carboxyphenoxy)propane (CPP) were synthesized for use in advanced drug delivery applications. PEG (M-n = 8000 Da) was incorporated to reduce polymeric particle clearance rates by the immune system and improve particle resuspension and aerosolization efficiencies. CPP and SA were selected to render the polymer insoluble in water and allow control over polymer degradation and drug release rates. In particular, CPP incorporation caused a significant decrease in polymer degradation rates and release kinetics of model drugs incorporated into poly(ether-anhydride) microparticles. Terpolymers were synthesized with weight-average molecular weights over 65 kDa without catalyst. The first thermal transition in polymers containing less than or equal to 10 wt % PEG was similar to80 degreesC (well above typical storage conditions and body temperature), and there was no evidence of a glass transition (-100 to 200 degreesC). Several of the polymers were used to produce particles suitable for injection or inhalation; these particles released model drugs, with molecular weights ranging from 443 to 5 143 000 Da, in a continuous fashion for up to 7 days.