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liberation of cytotoxic drugs was scarcely observed from
dendrimers conjugated via amide bonds (38).
CONCLUSION
The findings in this study suggest that the reduction of pI to
5 to 6 would be appropriate to reduce nonspecific accumulation
and prolong circulation time of PAMAM dendrimers. This study
also indicates that γ-glutamyl PAMAM dendrimers would
constitute versatile precursors to prepare PAMAM-based target-
ing devices even when targeting molecules and/or drugs of
positive charges are used. This modification may also be useful
to facilitate the release of drugs that are covalently conjugated
with the primary amine residues of R-glutamic acids via amino
acids (39) or a lysomotropic linkage (36, 37) (40-42) in
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ACKNOWLEDGMENT
The authors thank Mr. Takio Kobayashi for financial support. This
study was also supported by Grants-in-Aid for Scientific Research (B)
and for Exploratory Research, and Special Funds for Education and
Research (Development of SPECT Probes for Pharmaceutical In-
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