Formulation and characterization of poly (β amino ester) microparticles for genetic vaccine delivery

Steven R. Little, David M. Lynn, Sidharth V. Puram, Robert Langer

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Microparticulate delivery systems are a promising and versatile enhancement to DNA vaccines because they can target large payloads of plasmid and immunomodulating materials to antigen presenting cells (APC). A pH sensitive poly-β amino ester (PBAE) has been recently described which substantially increases adjuvancy and delivery efficiency of such microparticle formulations. This work describes the characterization and formulation considerations specific to these PBAE containing microparticles. PBAE increases the supercoiled content and overall effective loading of plasmid DNA. This polymer also significantly buffers the pH microenvironment created by ester bond degradation, rendering encapsulated plasmid more suitable for transfection. Release of plasmid from microparticles is controllable based on the amount of PBAE in the composition. Transfection is dependant upon phagocytosis, and is optimal for 15% and 25% PBAE microparticle formulations. However, larger quantities of PBAE may be toxic to cells indicating that the 15% PBAE formulation is a suitable candidate for delivery in future studies with disease specific, DNA vaccines.

Original languageEnglish
Pages (from-to)449-462
Number of pages14
JournalJournal of Controlled Release
Volume107
Issue number3
DOIs
StatePublished - Oct 20 2005
Externally publishedYes

Keywords

  • Controlled release
  • Genetic vaccination
  • Microencapsulation
  • Non-viral gene delivery
  • Poly-(lactic/glycolic) acid

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