Effect of alginate microencapsulation on the catalytic efficiency and in vitro enzyme-prodrug therapeutic efficacy of cytosine deaminase and of recombinant E. coli expressing cytosine deaminase

Michael G. Funaro, Krishnamurthy V. Nemani, Zhihang Chen, Zaver M. Bhujwalla, Karl E. Griswold, Barjor Gimi

Research output: Contribution to journalArticlepeer-review

Abstract

Cytosine deaminase (CD) catalyses the enzymatic conversion of the non-toxic prodrug 5-fluorocytosine (5-FC) to the potent chemotherapeutic form, 5-fluorouracil (5-FU). Intratumoral delivery of CD localises chemotherapy dose while reducing systemic toxicity. Encapsulation in biocompatible microcapsules immunoisolates CD and protects it from degradation. We report on the effect of alginate encapsulation on the catalytic and functional activity of isolated CD and recombinant E. coli engineered to express CD (E. coliCD). Alginate microcapsules containing either CD or Escherichia coliCD were prepared using ionotropic gelation. Conversion of 5-FC to 5-FU was quantitated in unencapsulated and encapsulated CD/E. coliCD using spectrophotometry, with a slower rate of conversion observed following encapsulation. Both encapsulated CD/5-FC and E. coliCD/5-FC resulted in cell kill and reduced proliferation of 9 L rat glioma cells, which was comparable to direct 5-FU treatment. Our results show that encapsulation preserves the therapeutic potential of CD and E. coliCD is equally effective for enzyme-prodrug therapy.

Original languageEnglish (US)
Pages (from-to)64-70
Number of pages7
JournalJournal of Microencapsulation
Volume33
Issue number1
DOIs
StatePublished - Jan 2 2016

Keywords

  • 5-fluorocytosine
  • 5-fluorouracil
  • Enzyme-prodrug therapy
  • alginate microcapsules
  • enzyme immobilisation

ASJC Scopus subject areas

  • Bioengineering
  • Pharmaceutical Science
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of 'Effect of alginate microencapsulation on the catalytic efficiency and in vitro enzyme-prodrug therapeutic efficacy of cytosine deaminase and of recombinant E. coli expressing cytosine deaminase'. Together they form a unique fingerprint.

Cite this