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PDT for viral and fungal infections
Abstracts / Photodiagnosis and Photodynamic Therapy 17 (2017) A4–A78
Antimicrobial PDT Oral OA-018 PDT for viral and fungal infections C. Kurachi Sao Carlos Institute of Physics, University of Sao Paulo, Brazil Photodynamic therapy (PDT) is mainly known as a local cancer treatment alternative, but more recently, its application for the microorganism control in infected lesions, also named as photodynamic inactivation (PDI), has been getting increased clinical interest. Presently, main applications are for the treatment of bacterial infections, as in infected ulcers and in periodontitis and endondontics. Even though, the treatment of viral and fungal infections show higher resistance to photodynamic action, PDT protocols have been developed and validated for these pathologies. Our group has been investigating the efficacy of PDT protocols for the treatment of several types of infections. In vitro experiments are performed to choose the best photosensitizer conditions (type, concentration, delivery, and drug/light interval) and illumination (wavelength, irradiance and fluence) parameters. The best parameters evaluated by confocal microscopy and microbiological tests are then investigated in animal models or directly in clinical trials. Instrumentation also plays an important role for a PDT success since a uniform illumination achieving a threshold dose for the microorganism inactivation must be obtained. Illumination planning includes the light delivery strategy and understanding of the light distribution within the infected lesion. In this talk, the PDT results for the treatment of pythiosis, onychomycosis, and HPV-related cervical lesions will be presented, discussing our strategies on defining the best protocols, light source development, and the clinical results. Acknowledgements: Financial support provided by FAPESP (CEPOF-CEPID Program) and CNPq.
A11
In this context, we propose the use of an innovative illumination scheme, by means of an ingestible luminous capsule to perform intra-gastric photodynamic therapy against Hp in a minimallyinvasive and efficient way [3]. By combining photonics and robotics, we have started by designing a miniaturized device whose geometrical, mechanical and light-emission properties were compatible with an efficient bacterial photo-killing and all the safety requirements for medical devices. During its permanence in the gastric antrum, where Hp is mostly found, the capsule illuminates the gastric wall thanks to Light Emitting Diode (LED) sources, powered by a built-in battery. No active controls are envisaged, neither for the illumination (ideally performed with a “360◦ scheme”) nor for the capsule positioning, to maximize the radiant energy delivered. Once in the intestine, the device will be turned off thanks to e.g. pH sensors. In this communication, the characteristics of the prototypes realized up to now will be described, including the illustration of their light-emission properties. Preliminary results in terms of in vivo photo-killing efficiency and safety studies will be presented. Besides, a semi-theoretical approach for the study of the action spectrum for in vivo photo-killing will be shown, where the gastric wall light-filtering and diffusing effect are taken into account. This has led to the definition of the best illumination wavelengths to optimize the PDT efficiency during the permanence time of the capsule in the stomach. The efforts in designing and realizing our device have led to the creation of Probiomedica, a spinoff of both the University of Florence and the Scuola Superiore Sant’Anna in Pisa.
References [1] M.R. Hamblin, J. Viveiros, C. Yang, et al., Antimicrob. Agents Chemother. 49 (7) (2005) 2822–2827. [2] R.A. Ganz, J. Viveiros, Ahmad, et al., Lasers Surg. Med. 36 (4) (2005) 260–265. [3] G. Tortora, B. Orsini, P. Pecile, et al., IEEE/ASME TMECH, 2016 (in press).
http://dx.doi.org/10.1016/j.pdpdt.2017.01.026 http://dx.doi.org/10.1016/j.pdpdt.2017.01.025 Oral OA-019 Ingestible capsule for minimally-invasive intragastric PDT against Helicobacter pylori G. Romano 1,∗ , G. Tortora 2 , B. Orsini 1 , P. Faraoni 1 , A. Gnerucci 1 , S. Calusi 1 , A. Menciassi 2 , F. Fusi 1 1
Department of Clinical and Experimental Biomedical Sciences “Mario Serio”, University of Florence, Italy 2 The BioRobotics Institute, Polo Sant’Anna Valdera, Scuola Superiore Sant’Anna, Italy In the framework of bacterial infections, those associated with Helicobacter pylori (Hp) are among those raising greatest concern, as they show a high worldwide prevalence combined with high failure of pharmacologic solutions due to antibiotic resistance. To overcome this limitation, endoscopic PDT devices have been tested, e.g. in the form of modified gastroscopes, also taking advantage from the endogenous production of photoactive porphyrins by the bacterium itself. In scientific literature, the proof-of-principle of Hp killing by visible light has been demonstrated in in vitro models [1] and in one case also in vivo with a clinical test [2]. However, all the illumination techniques realized up-to-date exhibit clear disadvantages, namely great invasivity, poor patient compliance and adverse effects.
Oral OA-020 Enhancement of photobactericidal activity of Chlorin-e6 grafted on cellulose nanocrystals by covalent coupling of polymyxin B F. Le Guern ∗ , T.S. Ouk, E. Poli, K. Grenier, V. Sol Laboratoire de Chimie des Sciences Naturelles LCSN, EA 1069, Université de Limoges, France Wound infection is a prominent topic in hospitals. Infections may delay wound healing, increasing the cost of treatment and in some cases lead to the patient’s death [1]. The emergence of antibiotic-resistant bacteria or superbugs makes infected wounds more difficult to cure. The bacteria responsible of infected wounds come from surroundings or from normal flora of the skin. Additionally, bacteria can form biofilms resulting to an increased resistance to conventional antimicrobial treatment. Therefore, new approaches had to be developed in order to overcome this problem. Antimicrobial photodynamic therapy (aPDT) is a promising alternative to eradicate microbes and has already inspired the development of innovative materials. Interesting results were achieved against Gram-positive bacteria [2], but it also appeared that Gram-negative strains, especially Pseudomonas aeruginosa, were less sensitive to aPDT. In previous studies, an enhanced efficacy of aPDT against Gram-negative bacteria was obtained by binding photosensitizers to antimicrobial peptides [3].
Antimicrobial PDT Oral OA-018 PDT for viral and fungal infections C. Kurachi Sao Carlos Institute of Physics, University of Sao Paulo, Brazil Photodynamic therapy (PDT) is mainly known as a local cancer treatment alternative, but more recently, its application for the microorganism control in infected lesions, also named as photodynamic inactivation (PDI), has been getting increased clinical interest. Presently, main applications are for the treatment of bacterial infections, as in infected ulcers and in periodontitis and endondontics. Even though, the treatment of viral and fungal infections show higher resistance to photodynamic action, PDT protocols have been developed and validated for these pathologies. Our group has been investigating the efficacy of PDT protocols for the treatment of several types of infections. In vitro experiments are performed to choose the best photosensitizer conditions (type, concentration, delivery, and drug/light interval) and illumination (wavelength, irradiance and fluence) parameters. The best parameters evaluated by confocal microscopy and microbiological tests are then investigated in animal models or directly in clinical trials. Instrumentation also plays an important role for a PDT success since a uniform illumination achieving a threshold dose for the microorganism inactivation must be obtained. Illumination planning includes the light delivery strategy and understanding of the light distribution within the infected lesion. In this talk, the PDT results for the treatment of pythiosis, onychomycosis, and HPV-related cervical lesions will be presented, discussing our strategies on defining the best protocols, light source development, and the clinical results. Acknowledgements: Financial support provided by FAPESP (CEPOF-CEPID Program) and CNPq.
A11
In this context, we propose the use of an innovative illumination scheme, by means of an ingestible luminous capsule to perform intra-gastric photodynamic therapy against Hp in a minimallyinvasive and efficient way [3]. By combining photonics and robotics, we have started by designing a miniaturized device whose geometrical, mechanical and light-emission properties were compatible with an efficient bacterial photo-killing and all the safety requirements for medical devices. During its permanence in the gastric antrum, where Hp is mostly found, the capsule illuminates the gastric wall thanks to Light Emitting Diode (LED) sources, powered by a built-in battery. No active controls are envisaged, neither for the illumination (ideally performed with a “360◦ scheme”) nor for the capsule positioning, to maximize the radiant energy delivered. Once in the intestine, the device will be turned off thanks to e.g. pH sensors. In this communication, the characteristics of the prototypes realized up to now will be described, including the illustration of their light-emission properties. Preliminary results in terms of in vivo photo-killing efficiency and safety studies will be presented. Besides, a semi-theoretical approach for the study of the action spectrum for in vivo photo-killing will be shown, where the gastric wall light-filtering and diffusing effect are taken into account. This has led to the definition of the best illumination wavelengths to optimize the PDT efficiency during the permanence time of the capsule in the stomach. The efforts in designing and realizing our device have led to the creation of Probiomedica, a spinoff of both the University of Florence and the Scuola Superiore Sant’Anna in Pisa.
References [1] M.R. Hamblin, J. Viveiros, C. Yang, et al., Antimicrob. Agents Chemother. 49 (7) (2005) 2822–2827. [2] R.A. Ganz, J. Viveiros, Ahmad, et al., Lasers Surg. Med. 36 (4) (2005) 260–265. [3] G. Tortora, B. Orsini, P. Pecile, et al., IEEE/ASME TMECH, 2016 (in press).
http://dx.doi.org/10.1016/j.pdpdt.2017.01.026 http://dx.doi.org/10.1016/j.pdpdt.2017.01.025 Oral OA-019 Ingestible capsule for minimally-invasive intragastric PDT against Helicobacter pylori G. Romano 1,∗ , G. Tortora 2 , B. Orsini 1 , P. Faraoni 1 , A. Gnerucci 1 , S. Calusi 1 , A. Menciassi 2 , F. Fusi 1 1
Department of Clinical and Experimental Biomedical Sciences “Mario Serio”, University of Florence, Italy 2 The BioRobotics Institute, Polo Sant’Anna Valdera, Scuola Superiore Sant’Anna, Italy In the framework of bacterial infections, those associated with Helicobacter pylori (Hp) are among those raising greatest concern, as they show a high worldwide prevalence combined with high failure of pharmacologic solutions due to antibiotic resistance. To overcome this limitation, endoscopic PDT devices have been tested, e.g. in the form of modified gastroscopes, also taking advantage from the endogenous production of photoactive porphyrins by the bacterium itself. In scientific literature, the proof-of-principle of Hp killing by visible light has been demonstrated in in vitro models [1] and in one case also in vivo with a clinical test [2]. However, all the illumination techniques realized up-to-date exhibit clear disadvantages, namely great invasivity, poor patient compliance and adverse effects.
Oral OA-020 Enhancement of photobactericidal activity of Chlorin-e6 grafted on cellulose nanocrystals by covalent coupling of polymyxin B F. Le Guern ∗ , T.S. Ouk, E. Poli, K. Grenier, V. Sol Laboratoire de Chimie des Sciences Naturelles LCSN, EA 1069, Université de Limoges, France Wound infection is a prominent topic in hospitals. Infections may delay wound healing, increasing the cost of treatment and in some cases lead to the patient’s death [1]. The emergence of antibiotic-resistant bacteria or superbugs makes infected wounds more difficult to cure. The bacteria responsible of infected wounds come from surroundings or from normal flora of the skin. Additionally, bacteria can form biofilms resulting to an increased resistance to conventional antimicrobial treatment. Therefore, new approaches had to be developed in order to overcome this problem. Antimicrobial photodynamic therapy (aPDT) is a promising alternative to eradicate microbes and has already inspired the development of innovative materials. Interesting results were achieved against Gram-positive bacteria [2], but it also appeared that Gram-negative strains, especially Pseudomonas aeruginosa, were less sensitive to aPDT. In previous studies, an enhanced efficacy of aPDT against Gram-negative bacteria was obtained by binding photosensitizers to antimicrobial peptides [3].