PEGylated recombinant human tumor necrosis factor alpha: pharmacokinetics and anti-tumor effects.
The aim of the present work was to investigate and assess the merit of PEGylated recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) following our previous work. The rHuTNF-alpha was modified using activated polyethylene glycol (PEG), N-succinimidyl succinnate monomethoxy polyethylene glycol (SS-PEG). The pharmacokinetics and anti-tumor effect were investigated. The experimental results showed that PEGylated rHuTNF-alpha could obviously alter in vivo behavioral characteristics of rHuTNF-alpha. Among the synthesized PEG-rHuTNF-alphas with different PEG molecules, PEG20000-rHuTNF-alpha demonstrated the longest circulating half-life (24.8 h) which was about 50 times longer than that of rHuTNF-alpha (28.8 min). In addition, there was much more PEG20000-rHuTNF-alpha distributed into tumor tissues than other PEG-rHuTNF-alphas or rHuTNF-alpha with time, and PEG20000-rHuTNF-alpha also showed the highest anti-tumor potency. These results indicated that PEG20000-rHuTNF-alpha was a useful long circulating molecule with selective localization in tumor tissues and enhanced anti-tumor activity of rHuTNF-alpha.
Li
Y P
YP
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 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
Gao
X J
XJ
Zhu
J H
JH
D000818:Animals; D005260:Female; D006207:Half-Life; D006801:Humans; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols