Development of novel oral formulations prepared via hot melt extrusion for targeted delivery of photosensitizer to the colon

Corona M Cassidy, Michael M Tunney, Deborah L Caldwell, Gavin P Andrews, Ryan F Donnelly

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Colon-residing bacteria, such as vancomycin-resistant Enterococcus faecalis and Bacteroides fragilis, can cause a range of serious clinical infections. Photodynamic antimicrobial chemotherapy (PACT) may be a novel treatment option for these multidrug resistant organisms. The aim of this study was to formulate a Eudragit®-based drug delivery system, via hot melt extrusion (HME), for targeting colonic release of photosensitizer. The susceptibility of E. faecalis and B. fragilis to PACT mediated by methylene blue (MB), meso-tetra(N-methyl-4-pyridyl)porphine tetra-tosylate (TMP), or 5-aminolevulinic acid hexyl-ester (h-ALA) was determined, with tetrachlorodecaoxide (TCDO), an oxygen-releasing compound, added in some studies. Results show that, for MB, an average of 30% of the total drug load was released over a 6-h period. For TMP and h-ALA, these values were 50% and 16% respectively. No drug was released in the acidic media. Levels of E. faecalis and B. fragilis were reduced by up to 4.67 and 7.73 logs, respectively, on PACT exposure under anaerobic conditions, with increased kill associated with TCDO. With these formulations, photosensitizer release could potentially be targeted to the colon, and colon-residing pathogens killed by PACT. TCDO could be used in vivo to generate oxygen, which could significantly impact on the success of PACT in the clinic.
Original languageEnglish
Pages (from-to)867-76
Number of pages10
JournalPhotochemistry and Photobiology
Volume87
Issue number4
DOIs
Publication statusPublished - 2011

Bibliographical note

© 2011 U.S. Government. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

Keywords

  • Administration, Oral
  • Aminolevulinic Acid
  • Anaerobiosis
  • Anti-Bacterial Agents
  • Bacteroides fragilis
  • Chlorine
  • Colon
  • Drug Compounding
  • Drug Delivery Systems
  • Drug Synergism
  • Enterococcus faecalis
  • Hot Temperature
  • Humans
  • Hydrogen-Ion Concentration
  • Light
  • Methylene Blue
  • Models, Theoretical
  • Oxides
  • Photochemotherapy
  • Photosensitizing Agents
  • Polymethacrylic Acids
  • Porphyrins
  • Prodrugs

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