Premium
The analysis of the transmission rate of locally administered siRNA to blood
Author(s) -
Kokuryo Toshio,
Yokoyama Yukihiro,
Nagino Masato
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.893.4
Subject(s) - small interfering rna , western blot , pharmacology , pharmacokinetics , chemistry , serine , kinase , downregulation and upregulation , medicine , cancer research , microbiology and biotechnology , transfection , biology , phosphorylation , biochemistry , gene
SiRNA is a promising therapeutic drug. Nek2 is a member of the serine/threonine kinase family. We previously reported the tumor suppressing effects of locally administered Nek2 siRNA (direct intra‐tumorous injection) in several cancer xenograft models. However, there is little information regarding to the pharmacokinetics of locally administered siRNA. This study sought to elucidate the transmission rate to blood and incidence of side effects after local administration of Nek2 siRNA in rat model. First, we mixed different amount of Nek2 siRNA with rat plasma (0, 1, 10, 100 and 500μM) and performed Northern blot analysis. Nek2 siRNA was detected in rat plasma in a concentration dependent manner. Next, the transmission of Nek2 siRNA to blood was evaluated after subcutaneous administration. Nek2 siRNA/biocollagen complexes were formed (500μM, 100μl) and were injected in femoral area. The blood was collected at different time point (5, 15, 30 and 60 min) and was analyzed by Northern blot. The detection of Nek2 siRNA in the blood was the highest at 15 min, and it disappeared within 1 h after the administration. There was no complication related to the local administration of Nek2 siRNA. Our data suggest that the local administration of siRNA is a safe delivery procedure with little cytotoxicity. However, further investigation will be needed for the future clinical application of siRNA.