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Int. J. Mol. Sci. 2015, 16(12), 29236-29249; doi:10.3390/ijms161226162

Intravenous Single-Dose Toxicity of Redaporfin-Based Photodynamic Therapy in Rodents

1
Luzitin SA, S. Martinho do Bispo, Coimbra 3045-016, Portugal
2
Bluepharma—Indústria Farmacêutica SA, S. Martinho do Bispo, Coimbra 3045-016, Portugal
3
Faculty of Chemistry, Jagiellonian University, Krakow 30-060, Poland
4
Chemistry Department, University of Coimbra, Coimbra 3004-535, Portugal
*
Author to whom correspondence should be addressed.
Academic Editors: Michael R. Hamblin and Ying-ying Huang
Received: 16 November 2015 / Revised: 30 November 2015 / Accepted: 2 December 2015 / Published: 8 December 2015
(This article belongs to the Special Issue Advances in Photodynamic Therapy)
View Full-Text   |   Download PDF [1031 KB, uploaded 8 December 2015]   |  

Abstract

We assessed the tolerability and safety in rodents of a single intravenous (i.v.) dose of redaporfin, a novel photosensitizer for Photodynamic Therapy (PDT) of cancer. Two approaches were used to evaluate acute toxicity: (i) a dose escalation study in BALB/c mice to evaluate the maximum tolerated dose of redaporfin; and (ii) a safety toxicology study in Wistar rats, of a single dose of redaporfin, with or without illumination, to evaluate possible signs of systemic toxicity. Redaporfin formulation was well tolerated by mice, with no signs of adverse reactions up to 75 mg/kg. In rats, there were no relevant changes, except for a significant, but transient, increase in the blood serum markers for hepatic function and muscle integrity, and also on neutrophil counts, observed after the application of light. The overall results showed that redaporfin-PDT is very well tolerated. No abnormalities were observed, including reactions at the injection site or skin phototoxicity, although the animals were maintained in normal indoor lighting. Redaporfin also showed a high efficacy in the treatment of male BALB/c mice with subcutaneously implanted colon (CT26) tumours. Vascular-PDT with 1.5 mg/kg redaporfin and a light dose of 74 J/cm2 led to the complete tumour regression in 83% of the mice. View Full-Text
Keywords: photodynamic therapy; cancer treatment; bacteriochlorin; redaporfin; intravenous formulation; single-dose toxicity; rodents photodynamic therapy; cancer treatment; bacteriochlorin; redaporfin; intravenous formulation; single-dose toxicity; rodents
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Rocha, L.B.; Schaberle, F.; Dąbrowski, J.M.; Simões, S.; Arnaut, L.G. Intravenous Single-Dose Toxicity of Redaporfin-Based Photodynamic Therapy in Rodents. Int. J. Mol. Sci. 2015, 16, 29236-29249.

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