Abstract
A series of biodegradable poly (ester-anhydride), Poly(sebacic anhydride-co-ethylene glycol), was prepared by melt condensation for use in advanced drug delivery applications. Sebacic acid, a hydrophobic monomer, was copolymerized with PEG in order to produce water-insoluble polymers capable of providing continuous drug release kinetics following immersion in an aqueous environment. Poly ethylene glycol(PEG) can reduce particle clearance from bloodstream by macrophages and was a FDA approved polymer. In this paper, we changed various amounts of PEG (15~35% by mass) incorporated into the backbone of the polymers to allow tuning of particle surface properties. The diblock copolymers were synthesized with the molecular weight range of 9,500~14,500 Da without any catalyst. Copolymers of higher molecular weights were obtained by increasing poly (sebacic anhydride) content. The self-assembly of this water-insoluble diblock copolymer formed nanoparticles by solvent displacement method. The mean diameters of micelles were less than 200nm and exhibited low polydispersity index. The degradation of polymeric micelles was studies by measuring the sebacic acid concentration in phosphate buffer. The result showed that a rapid degradation occurred during first 6 hr, followed by a slow degradation. After 5 days, about 70~80% of polymeric micelles core were degraded. The drug encapsulation efficiency and the in vitro drug release kinetics were measured by high-performance liquid chromatography (HPLC). Of all, the entrapment efficiency of taxol-loaded micelles were 10.31~40.51%. The longer hydrophobic chain was, the lower its entrapment efficiency was. The drug release from mPEGPSA nanoparticle was found to be biphasic with an initial burst of 60~70% during the first 2hr, followed by a sustained release with 100% accumulative drug release after 5 days.