Acta Pharmacologica Sinica 2005 February; 26 (2): 242-249; doi: 10.1111/j.1745-7254.2005.00537.x

Aim: To study the in vitro release of recombinant human tumor necrosis factor-alpha (rHuTNF-α) encapsulated in poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles, and investigate the influence of methoxypolyethyleneglycol (MePEG) molecular weight and particle size.

Methods: Three sizes (approximately 80, 170, and 240 nm) of PEG-PHDCA nanoparticles loading rHuTNF-α were prepared at different MePEG molecular weights (M_r =2000, 5000, and 10 000) using the double emulsion method. The in vitro rHuTNF-α release was studied in PBS and rat plasma.

Results: 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-α 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.

Conclusion: The MePEG molecular weight and particle size had an obvious influence on rHuTNF-α release. rHuTNF-α released from PEG-PHDCA nanoparticles in a diffusion-based pattern in PBS, but in a diffusion and erosion-controlled manner in rat plasma.

Keywords: tumor necrosis factor-alpha; stealth; nanoparticles; polyethylene glycols; poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate)