Stealth polycyanoacrylate nanoparticles as tumor necrosis factor-alpha carriers: pharmacokinetics and anti-tumor effects.
The objective of this study was to investigate the pharmacokinetics and in vivo anti-tumor effect of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) encapsulated in poly(methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles. Our experimental results showed that PEG-PHDCA nanoparticles could extend the half-life of rHuTNF-alpha to 7.42 h and obviously change the protein biodistribution in tissues, and in particular, increase accumulation of rHuTNF-alpha in tumor. Compared with PHDCA nanoparticles and free rHuTNF-alpha, PEG-PHDCA nanoparticles loaded with rHuTNF-alpha showed higher antitumor potency at the same dose, which might be related to its higher accumulation in tumor tissues and longer plasma circulation time. Therefore, PEG-PHDCA nanoparticles could be an effective carrier for 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
Zhou
J J
JJ
Gao
X J
XJ
Zhu
J H
JH
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003487:Cyanoacrylates / Q000008:administration & dosage*; D004337:Drug Carriers; D005260:Female; D006207:Half-Life; D006801:Humans; D051379:Mice; D011108:Polymers; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
D000970:Antineoplastic Agents; D003487:Cyanoacrylates; D004337:Drug Carriers; D011108:Polymers; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha