Polymer genomics: Shifting the gene and drug delivery paradigms

Alexander V. Kabanov, Elena V. Batrakova, Srikanth Sriadibhatla, Zhihui Yang, David Lee Kelly, Valery Yu Alakov

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Pluronic, the A-B-A amphiphilic block copolymers of poly(ethylene oxide) and poly(propylene oxide), can up-regulate the expression of selected genes in cells and alter genetic responses to antineoplastic agents in cancer. Two key new findings are discussed in relation to current drug and gene delivery strategies. First, these block copolymers alone and in combination with a polycation, polyethyleneimine, can up-regulate the expression of reporter genes in stably transfected cells. This underscores the ability of selected synthetic polymers to enhance transgene expression through a mechanism that augments improved DNA delivery into a cell. Second, although, when used alone, Pluronic is "genetically benign," when combined with an antineoplastic agent, doxorubicin, it drastically alters pharmacogenomic responses to this agent and prevents the development of multidrug resistance in breast cancer cells. Collectively, these studies propose the need for a thorough assessment of pharmacogenomic effects of polymer therapeutics to maximize the clinical outcomes and understand the pharmacological and toxicological effects of polymer-based drugs and delivery systems.

Original languageEnglish (US)
Pages (from-to)259-271
Number of pages13
JournalJournal of Controlled Release
Volume101
Issue number1-3 SPEC. ISS.
DOIs
Publication statusPublished - Jan 3 2005

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Keywords

  • Anthracycline antibiotics
  • Block copolymer
  • Cancer
  • Gene delivery
  • Gene expression
  • Multidrug resistance
  • P-glycoprotein
  • Poloxamer

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Kabanov, A. V., Batrakova, E. V., Sriadibhatla, S., Yang, Z., Kelly, D. L., & Alakov, V. Y. (2005). Polymer genomics: Shifting the gene and drug delivery paradigms. Journal of Controlled Release, 101(1-3 SPEC. ISS.), 259-271. https://doi.org/10.1016/j.jconrel.2004.07.009