Abstract
Polyanhydrides have been used in many drug delivery systems due to their biodegradability and biocompatibility. Their degradation pattern of surface erosion made them suitable for stable drug release applications. However, in nanoparticle systems, this degradation pattern may not hold, and the drug release kinetics will be different also. In this study, 1,3-bis(p-carboxyphenoxy)propane (CPP) and sebacic acid (SA) were synthesized through melt-condensation into homopolymers and copolymers to investigate the different degradation patterns and drug release mechanisms of disk and nanoparticle. By solvent displacement and emulsification methods, the polymers were prepared into the nanoparticles with dimension in 200 nm through changing polymer concentrations, and verifying surfactants. PSA disks degraded for about two weeks wile nanoparticles displayed a fast degradation in about one week, depending on the preparation method. Besides the large differences of surface area to volume ratio between disks and nanoparticles, the micronization of the samples and nanoparticles preparation methods inducing decrease of the crystallinity of SA segments of these nanoparticles were important factors of tailoring degradation rates. The copolymers contained with hydrophobic segment of CPP did not preventing water penetrating into the samples to hinder hydrolysis but hindered the crystallization of SA segments, which resulting fast degradation of these nanoparticles. Camptothecin and paclitaxel, the highly hydrophobic anticancer drugs, were used as modeling drugs. The initial drug loading directly affected the drug loading efficiencies, and also the size of the nanoparticles. The results revealed that drugs themselves occupied the space in the nanoparticles. The drug loading efficiencies of the paclitaxel were over 10% based on polymer weight, which indicating polyanhydrides suitable for encapsulating paclitaxel. In the exams of encapsulation with camptothecin, the drug loading efficiencies and drug release mechanism were independent on the preparation methods. However, the preparation methods dominated the degradation of nanoparticles. The drug release of the nanoparticles all demonstrated an initial burst. In the meantime, the degradation of nanoparticles and drug release displayed significantly inconsistent, i.e. the drug release rates were faster then the nanoparticles degradation rates, the drug released in 2-3 days while degradation lasted for 3-4 days even longer. Besides the preparation methods of nanoparticles, the solvent evaporation procedure, the drug affecting polymer crystallization were also important factors on drug release and nanoparticle degradation.