PEGylated polycyanoacrylate nanoparticles as tumor necrosis factor-alpha carriers.
The aim of this study was to find an effective carrier for recombinant human tumor necrosis factor-alpha (rHuTNF-alpha). The influence of solvent systems containing poly(methoxy-polyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEGylated PHDCA) on the biological activity of rHuTNF-alpha was investigated. The PEGylated PHDCA nanoparticles loading rHuTNF-alpha were prepared with the double emulsion method. The influence of main experimental factors on the entrapment efficiency was evaluated by the Uniform Design. The physicochemical characteristics and in vitro release of rHuTNF-alpha from the nanoparticles were determined. The results showed that serum albumin such as human serum albumin (HSA) or bovine serum albumin (BSA) could play a protective action on rHuTNF-alpha in the preparation process. At > or =2.0% (w/v) HSA concentration, more 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 nanoparticles was about 60% and the nanoparticle size was about 150 nm. The nanoparticles were spherical in shape and uniform with the value of the zeta potential about -9 mV. The rHuTNF-alpha release from the nanoparticle showed an initial burst and then continued in a sustained fashion. The results showed that the PEGylated PHDCA nanoparticles could be an effective carrier for rHuTNF-alpha.
Li
Y P
YP
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China. ypli@mail.shcnc.ac.cn
Pei
Y Y
YY
Zhou
Z H
ZH
Zhang
X Y
XY
Gu
Z H
ZH
Ding
J
J
Zhou
J J
JJ
Gao
X J
XJ
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003487:Cyanoacrylates / Q000737:chemistry*; D004337:Drug Carriers; D004355:Drug Stability; D006801:Humans; D008863:Microspheres; D011092:Polyethylene Glycols / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D012995:Solubility; D012996:Solutions; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D003487:Cyanoacrylates; D004337:Drug Carriers; D011994:Recombinant Proteins; D012996:Solutions; D014409:Tumor Necrosis Factor-alpha; C121140:polyethyleneglycol polyhexadecylylcyanoacrylate copolymer; D011092:Polyethylene Glycols