Parallel synthesis and screening of polymers for nonviral gene delivery

Sutapa Barua, Amit Joshi, Akhilesh Banerjee, Dana Matthews, Susan T. Sharfstein, Steven M. Cramer, Ravi S. Kane, Kaushal Rege

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

We describe the parallel synthesis and in vitro evaluation of a cationic polymer library for the discovery of nonviral gene delivery vectors. The library was synthesized based on the ring-opening polymerization reaction between epoxide groups of diglycidyl ethers and the amines of (poly)amines. Parallel screening of soluble library constituents led to the identification of lead polymers with high DNA-binding efficacies. Transfection efficacies of lead polymers were evaluated using PC3-PSMA human prostate cancer cells and murine osteoblasts in the absence and presence of serum. In vitro experiments resulted in the identification of a candidate polymer that demonstrated significantly higher transfection efficacies and lower cytotoxicities than poly(ethyleneimine) (pEI), the current standard for polymeric transfection agents. In addition, polymers that demonstrated moderately higher and comparable transfection efficacies with respect to pEI were also identified. Our results demonstrate that high-throughput synthesis and screening of polymers is a powerful approach for the identification of novel nonviral gene delivery agents.

Original languageEnglish (US)
Pages (from-to)86-97
Number of pages12
JournalMolecular Pharmaceutics
Volume6
Issue number1
DOIs
Publication statusPublished - Feb 2 2009

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Keywords

  • Cationic polymers
  • Diglycidyl ethers
  • Dna-binding
  • Ethidium bromide
  • Nonviral gene delivery
  • Parallel screening
  • Parallel synthesis
  • Polyamines
  • Transfection

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Medicine
  • Drug Discovery

Cite this

Barua, S., Joshi, A., Banerjee, A., Matthews, D., Sharfstein, S. T., Cramer, S. M., ... Rege, K. (2009). Parallel synthesis and screening of polymers for nonviral gene delivery. Molecular Pharmaceutics, 6(1), 86-97. https://doi.org/10.1021/mp800151j