Effect of MePEG molecular weight and particle size on in vitro release of tumor necrosis factor-alpha-loaded nanoparticles1

Abstract

To study the in vitro release of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) encapsulated in poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles, and investigate the influence of methoxypolyethyleneglycol (MePEG) molecular weight and particle size. Three sizes (approximately 80, 170, and 240 nm) of PEG-PHDCA nanoparticles loading rHuTNF-alpha were prepared at different MePEG molecular weights (M(r) =2000, 5000, and 10,000) using the double emulsion method. The in vitro rHuTNF-alpha release was studied in PBS and rat plasma. A higher burst-release and cumulative-release rate were observed for nanoparticles with higher MePEG molecular weight or smaller particle size. A decreased cumulative release of rHuTNF-alpha following the initial burst effect was found in PBS, while the particle sizes remained constant and MePEG liberated. In contrast, in rat plasma, slowly increased cumulative-release profiles were obtained after the burst effect. During a 5-h incubation in rat plasma, more than 50% of the PEG-PHDCA nanoparticles degraded. The MePEG molecular weight and particle size had an obvious influence on rHuTNF-alpha release. rHuTNF-alpha released from PEG-PHDCA nanoparticles in a diffusion-based pattern in PBS, but in a diffusion and erosion-controlled manner in rat plasma.