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Photobac derived from bacteriochlorophyll-a shows potential for treating brain tumor in animal models by photodynamic therapy with desired pharmacokinetics and limited toxicity in rats and dogs.

Abstract
Photobac is a near infrared photosensitizer (PS) derived from naturally occurring bacteriochlorophyll- a, with a potential for treating a variety of cancer types (U87, F98 and C6 tumor cells in vitro). The main objective of the studies presented herein was to evaluate the efficacy, toxicity and pharmacokinetic profile of Photobac in animals (mice, rats and dogs) and submit these results to the United States Food and Drug Administration (US FDA) for its approval to initiate Phase I human clinical trials of glioblastoma, a deadly cancer disease with no long term cure. The photodynamic therapy (PDT) efficacy of Photobac was evaluated in mice subcutaneously implanted with U87 tumors, and in rats bearing C6 tumors implanted in brain. In both tumor types, the Photobac-PDT was quite effective. The long-term cure in rats was monitored by magnetic resonance imaging (MRI) and histopathology analysis. A detailed pharmacology, pharmacokinetics and toxicokinetic study of Photobac was investigated in both non-GLP and GLP facilities at variable doses following the US FDA parameters. Safety Pharmacology studies suggest that there is no phototoxicity, cerebral or retinal toxicity with Photobac. No metabolites of Photobac were observed following incubation in rat, dog, mini-pig and human hepatocytes. Based on current biological data, Photobac-IND received the approval for Phase-I human clinical trials to treat Glioblastoma (brain cancer), which is currently underway at our institute. Photobac has also received an orphan drug status from the US FDA, because of its potential for treating Glioblastoma as no effective treatment is currently available for this deadly disease.
AuthorsFarukh A Durrani, Joseph Cacaccio, Steven G Turowski, Mykhaylo Dukh, Wiam Bshara, Leslie Curtin, Sandra Sexton, Joseph A Spernyak, Ravindra K Pandey
JournalBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 168 Pg. 115731 (Dec 2023) ISSN: 1950-6007 [Electronic] France
PMID37857248 (Publication Type: Journal Article)
CopyrightCopyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Chemical References
  • Bacteriochlorophylls
  • Bacteriochlorophyll A
  • Photosensitizing Agents
Topics
  • Rats
  • Dogs
  • Animals
  • Mice
  • Humans
  • Swine
  • Bacteriochlorophylls (therapeutic use)
  • Glioblastoma (pathology)
  • Photochemotherapy (methods)
  • Bacteriochlorophyll A (therapeutic use)
  • Swine, Miniature
  • Brain Neoplasms (drug therapy, pathology)
  • Photosensitizing Agents (pharmacology, therapeutic use)
  • Models, Animal

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