title: PEGylated recombinant human tumor necrosis factor alpha: pharmacokinetics and anti-tumor effects.
abstract: 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.
authors: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China. ypli@mail.shcnc.ac.cn
authors: Y P
authors: YP
authors: Li
authors: Y Y
authors: YY
authors: Pei
authors: Z H
authors: ZH
authors: Zhou
authors: X Y
authors: XY
authors: Zhang
authors: Z H
authors: ZH
authors: Gu
authors: J
authors: J
authors: Ding
authors: X J
authors: XJ
authors: Gao
authors: J H
authors: JH
authors: Zhu
mesh_terms: 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*
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols