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Stealth dendrimers for drug delivery: correlation between PEGylation, cytocompatibility, and drug payload

  • Hu Yang
  • Stephanie T. Lopina
  • Linda P. DiPersio
  • Steven P. Schmidt
Article

Abstract

It is advantageous to utilize low generation polyamidoamine (PAMAM) dendrimers for drug delivery because low generations (generation 4.0 or below) have more biologically favorable properties as compared to high generations. Nevertheless, modification of low generation dendrimers with PEG to create stealth dendrimers is still necessary to avoid potential side effects by long term accumulation. However, low generation dendrimers have much fewer surface sites for drug loading as compared to higher generations. To efficiently utilize low generation dendrimer-based stealth dendrimers for drug loading, PEGylation needs to be optimized. In this study, we synthesized a series of stealth dendrimers based on low generation Starburst™ PAMAM dendrimers (i.e., G2.5, G3.0, G3.5, and G4.0) and quantitatively assessed PEGylation efficacy in modulating cytocompatibility of low generation PAMAM dendrimers. Cytocompatibility of stealth dendrimers was examined using endothelial cells. The results showed that PEGylation degree on low generation dendrimers could be dramatically reduced to leave as many unoccupied surface groups as possible for drug loading, while maintaining the drug carrier cytocompatibility. 3PEGs-G3.0 and 10PEGs-G4.0 were considered initially optimized stealth dendrimers that would be further modified to deliver drugs of interest. Correlation of PEGylation, cytocompatibility, and drug payload allowed us to optimize low generation dendrimer-based stealth dendrimers for drug delivery and advance the understanding of structure-property relationship of stealth dendrimers.

Keywords

Drug Loading Surface Group PAMAM Dendrimers Fresh Growth Medium Endothelial Cell Growth Medium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Hu Yang acknowledges the new faculty startup support from the Department of Biomedical Engineering and School of Engineering of Virginia Commonwealth University. Stephanie Lopina acknowledges the support from an NSF CAREER award (BES-9984840), a University of Akron Faculty Research Grant (FRG-1484), and a Sigma Xi Grant-in-Aid of Research.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Hu Yang
    • 1
  • Stephanie T. Lopina
    • 2
    • 3
  • Linda P. DiPersio
    • 4
  • Steven P. Schmidt
    • 4
  1. 1.Department of Biomedical Engineering Virginia Commonwealth UniversityRichmondUSA
  2. 2.Department of Chemical and Biomolecular Engineering The University of Akron AkronUSA
  3. 3.Department of Biomedical Engineering The University of Akron AkronUSA
  4. 4.Falor Division of Surgical Research Akron City Hospital, Summa Health SystemAkronUSA

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