Abstract:
The impact of water-soluble and amphiphilic polymers with different structures, namely carboxymethyl cellulose (CMC), polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), was studied on the photoactivity of chlorin photosensitizers (PSs) in photodynamic therapy (PDT). It was shown that such polymers can cause a considerable increase in the PS activity, both in the process of singlet oxygen photogeneration in cell experiments, and in the model reaction of a substrate photooxidation in water. Amongst the studied polymers, CMC and PVP appeared to have the most significant influence on the photoactivity of PSs. The observed effect of the polymers on the photosensitizing activity of PSs can be attributed to the presence of chlorin-polymer interactions resulting in the porphyrin disaggregation in aqueous phase. The effect of the polymers on the photocytotoxicity of PSs is attributed to the absence of interactions between chlorin and polypeptide or lipoproteins which results in a decrease of the photoactivity of chlorins in cell culture. The PS/polymer systems appear to be a new effective dosage form of PDT drugs.
Zusammenfassung:
Die Wirkung von wasserlöslichen und amphiphilen Polymeren mit unterschiedlichen Strukturen (Carboxymethylcellulose, CMC; Polyvinylalkohol, PVA; Polyvinylpyrrolidon, PVP), auf die Photoaktivität von Chlorin-Photosensibilisatoren (PS) in der photodynamischen Therapie (PDT) wurde untersucht. Es wurde gezeigt, dass solche Polymere eine erhebliche Steigerung der PS-Aktivität bewirken können, sowohl im Prozess der Singulett-Sauerstoff-Generation in Zellexperimenten als auch in der Modellreaktion einer Substrat-Photooxidation in Wasser. Unter den untersuchten Polymeren schienen CMC und PVP den größten signifikanten Einfluss auf die Photoaktivität der PS zu haben. Die beobachtete Wirkung der Polymere auf die photosensibilisierende Aktivität der PS kann auf das Vorhandensein von Chlorin-Polymer-Wechselwirkungen zurückgeführt werden, die in einer Porphyrin-Disaggregation in wässriger Phase resultieren. Die Wirkung der Polymere auf die Photozytotoxizität der PS wiederum ist auf das Fehlen von Wechselwirkungen zwischen Chlorin und Polypeptid bzw. Lipoproteinen zurückzuführen, die zu einer Abnahme der Photoaktivität von Chlorin in der Zellkultur führt. Die PS/Polymer-Systeme scheinen eine neue wirksame Darreichungsform von PDT-Medikamenten zu sein.
This work was supported by the Russian Foundation for Basic Research (projects numbers 13-03-00429-a, 11-02-01090-a and 11-03-12074-ofi-m). The PS/polymer formulations were generously prepared by N. N. Glagolev (Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia). NIH-3T3-EWS-FLI1 mouse fibroblasts were a generous gift of Prof. C. Malvy (Institut Gustave Roussy, Villejuif, France). The photodynamic activity of HBL-100 and Skov-3 cells was studied by E. Yu. Filinova (N. N. Blokhin Cancer Research Center, Russian Academy of Medical Sciences).
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