2012 Fiscal Year Final Research Report
PEGylation of Protein Drugs utilizing the Complexation with Cyclodextrin
| Project/Area Number |
23890161
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
HIGASHI Taishi 熊本大学, 大学院・生命科学研究部, 助教 (20613409)
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| Project Period (FY) |
2011 – 2012
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| Keywords | シクロデキストリン / ポリエチレングリコール / タンパク質 / 超分子 / 制御放出 |
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| Research Abstract |
The purpose of this study is to design the reversible PEGylation of proteins throughthe interaction of cyclodextrin (CyD) and guest-molecule modified polyethylene glycol(PEG). First, we prepared the insulin conjugate with glucuronylglucosyl- -CyD (GUG- -CyD). Thermostability and enzymatic stability of the conjugate were improved compared toinsulin alone. However, the hypoglycemic effect of the insulin was lost by theconjugation with GUG- -CyD.Next, we prepared insulin conjugate with guest-molecule (adamantane), and thisconjugate retained the activity compared to intact insulin. In addition, supramolecularPEGylated insulin, consisting insulin/adamantine conjugate and PEGylated -CyD showedprolonged hypoglycemic effect compared to insulin alone and insulin/adamantineconjugate.The results suggest that supramolecular PEGylation increases circulating half-life ofprotein drugs without loss of the activity.
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