DNA Vaccine Delivery from Poly(ortho ester) Microspheres

Chun Wang, Herman N. Eisen, Robert Langer, Jorge Heller

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Biodegradable poly(ortho ester) microspheres designed specifically to deliver plasmid DNA to antigen-presenting cells (APCs) were prepared. Poly(ortho esters) degrade hydrolytically to non-toxic products and, most importantly, do not generate an acidic environment that could adversely affect plasmid DNA bioactivity. Two types of poly(ortho esters) were prepared. One type (POE 1) lacks tertiary amine groups in the polymer backbone, while the other type (POE 2) has tertiary amines in the polymer backbone. In vitro experiments have shown that at pH 7.4, both polymers release plasmid DNA at a slow, steady rate, but when the pH is abruptly changed to 5.0 to simulate the environment within the phagosomes, both polymers rapidly released DNA. The rapid release of plasmid DNA at pH 5 is due to the known pH-dependent rate of poly-(ortho ester) hydrolysis. While POE 1 rapidly released DNA as soon as the pH was lowered, POE 2 released plasmid DNA only after a 24-h induction period. Both polymers were found to suppress the growth of tumor cells bearing a model antigen, but POE 2 was significantly more effective than POE 1. The greater effectiveness of POE 2 is due to the delay in plasmid DNA release that prevents release before the APCs become activated and reach the lymph nodes. The delay in plasmid DNA release is most likely due to an electrostatic interaction between the negative charges on the plasmid DNA and the positive charges on POE 2 created when the tertiary amines become protonated at the low pH therefore well suited as biopharmaceutical.

Original languageEnglish (US)
Title of host publicationModern Biopharmaceuticals
Subtitle of host publicationDesign, Development and Optimization
PublisherWiley-VCH Verlag GmbH
Pages1487-1506
Number of pages20
Volume4
ISBN (Print)352731184X, 9783527311842
DOIs
StatePublished - Feb 5 2008

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Keywords

  • Biocompatibility
  • Biodegradable
  • Electrophoresis
  • Microspheres
  • Transgenic mice

Cite this

Wang, C., Eisen, H. N., Langer, R., & Heller, J. (2008). DNA Vaccine Delivery from Poly(ortho ester) Microspheres. In Modern Biopharmaceuticals: Design, Development and Optimization (Vol. 4, pp. 1487-1506). Wiley-VCH Verlag GmbH. https://doi.org/10.1002/9783527620982.ch61