PEGylated polycyanoacrylate nanoparticles as tumor necrosis factor-alpha carriers

The aim of this study was to find an effective carrier for recombinant huma n tumor necrosis factor-alpha (rHuTNF-alpha). The influence of solvent syst ems containing poly(methoxy-polyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEGylated PHDCA) on the biological activity of rHuTNF-alph a was investigated. The PEGylated PHDCA nanoparticles loading rHuTNF-alpha were prepared with the double emulsion method. The influence of main experi mental factors on the entrapment efficiency was evaluated hy the Uniform De sign. The physicochemical characteristics and in vitro release of rHuTNF-al pha from the nanoparticles were determined. The results showed that serum a lbumin such as human serum albumin (HSA) or bovine serum albumin (BSA) coul d play a protective action on rHuTNF-alpha in the preparation process. At g reater than or equal to2.0% (w/v) HSA concentration, mon than 85% of rHuTNF -alpha activity remained and the role of HSA was not affected by copolymer concentrations from 0.5 to 3.0% (w/v). The entrapment efficiency of the nan oparticles was about 60% and the nanoparticle size was about 150 nm. The na noparticles were spherical in shape and uniform with the value of the zeta potential about -9 mV. The rHuTNF-alpha release from the nanoparticle showe d an initial burst and then continued in a sustained fashion. The results s howed that the PEGylated PHDCA nanoparticles could be an effective carrier for rHuTNF-alpha. (C) 2001 Elsevier Science B.V. All rights reserved.