Effectiveness of antimicrobial photodynamic therapy with a single treatment of RLP068/Cl in an experimental model of Staphylococcus aureus wound infection

Authors

  • O. Simonetti,

    1. Dermatological Clinic, Department of Clinical Medicine and Applied Biotechnology, Università Politecnica delle Marche, Ancona, Italy
      *Institute of Infectious Diseases and Public Health and ¶Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy
      †Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA–IRCCS, Ancona, Italy
      ‡Molteni Therapeutics, Siena, Italy
      §Histology, Department of Molecular Pathology and Innovative Therapies, Università Politecnica delle Marche, Ancona, Italy
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  • O. Cirioni,

    1. Dermatological Clinic, Department of Clinical Medicine and Applied Biotechnology, Università Politecnica delle Marche, Ancona, Italy
      *Institute of Infectious Diseases and Public Health and ¶Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy
      †Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA–IRCCS, Ancona, Italy
      ‡Molteni Therapeutics, Siena, Italy
      §Histology, Department of Molecular Pathology and Innovative Therapies, Università Politecnica delle Marche, Ancona, Italy
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  • F. Orlando,

    1. Dermatological Clinic, Department of Clinical Medicine and Applied Biotechnology, Università Politecnica delle Marche, Ancona, Italy
      *Institute of Infectious Diseases and Public Health and ¶Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy
      †Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA–IRCCS, Ancona, Italy
      ‡Molteni Therapeutics, Siena, Italy
      §Histology, Department of Molecular Pathology and Innovative Therapies, Università Politecnica delle Marche, Ancona, Italy
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  • C. Alongi,

    1. Dermatological Clinic, Department of Clinical Medicine and Applied Biotechnology, Università Politecnica delle Marche, Ancona, Italy
      *Institute of Infectious Diseases and Public Health and ¶Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy
      †Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA–IRCCS, Ancona, Italy
      ‡Molteni Therapeutics, Siena, Italy
      §Histology, Department of Molecular Pathology and Innovative Therapies, Università Politecnica delle Marche, Ancona, Italy
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  • G. Lucarini,

    1. Dermatological Clinic, Department of Clinical Medicine and Applied Biotechnology, Università Politecnica delle Marche, Ancona, Italy
      *Institute of Infectious Diseases and Public Health and ¶Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy
      †Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA–IRCCS, Ancona, Italy
      ‡Molteni Therapeutics, Siena, Italy
      §Histology, Department of Molecular Pathology and Innovative Therapies, Università Politecnica delle Marche, Ancona, Italy
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  • C. Silvestri,

    1. Dermatological Clinic, Department of Clinical Medicine and Applied Biotechnology, Università Politecnica delle Marche, Ancona, Italy
      *Institute of Infectious Diseases and Public Health and ¶Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy
      †Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA–IRCCS, Ancona, Italy
      ‡Molteni Therapeutics, Siena, Italy
      §Histology, Department of Molecular Pathology and Innovative Therapies, Università Politecnica delle Marche, Ancona, Italy
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  • A. Zizzi,

    1. Dermatological Clinic, Department of Clinical Medicine and Applied Biotechnology, Università Politecnica delle Marche, Ancona, Italy
      *Institute of Infectious Diseases and Public Health and ¶Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy
      †Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA–IRCCS, Ancona, Italy
      ‡Molteni Therapeutics, Siena, Italy
      §Histology, Department of Molecular Pathology and Innovative Therapies, Università Politecnica delle Marche, Ancona, Italy
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  • L. Fantetti,

    1. Dermatological Clinic, Department of Clinical Medicine and Applied Biotechnology, Università Politecnica delle Marche, Ancona, Italy
      *Institute of Infectious Diseases and Public Health and ¶Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy
      †Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA–IRCCS, Ancona, Italy
      ‡Molteni Therapeutics, Siena, Italy
      §Histology, Department of Molecular Pathology and Innovative Therapies, Università Politecnica delle Marche, Ancona, Italy
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  • G. Roncucci,

    1. Dermatological Clinic, Department of Clinical Medicine and Applied Biotechnology, Università Politecnica delle Marche, Ancona, Italy
      *Institute of Infectious Diseases and Public Health and ¶Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy
      †Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA–IRCCS, Ancona, Italy
      ‡Molteni Therapeutics, Siena, Italy
      §Histology, Department of Molecular Pathology and Innovative Therapies, Università Politecnica delle Marche, Ancona, Italy
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  • A. Giacometti,

    1. Dermatological Clinic, Department of Clinical Medicine and Applied Biotechnology, Università Politecnica delle Marche, Ancona, Italy
      *Institute of Infectious Diseases and Public Health and ¶Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy
      †Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA–IRCCS, Ancona, Italy
      ‡Molteni Therapeutics, Siena, Italy
      §Histology, Department of Molecular Pathology and Innovative Therapies, Università Politecnica delle Marche, Ancona, Italy
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  • A. Offidani,

    1. Dermatological Clinic, Department of Clinical Medicine and Applied Biotechnology, Università Politecnica delle Marche, Ancona, Italy
      *Institute of Infectious Diseases and Public Health and ¶Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy
      †Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA–IRCCS, Ancona, Italy
      ‡Molteni Therapeutics, Siena, Italy
      §Histology, Department of Molecular Pathology and Innovative Therapies, Università Politecnica delle Marche, Ancona, Italy
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  • M. Provinciali

    1. Dermatological Clinic, Department of Clinical Medicine and Applied Biotechnology, Università Politecnica delle Marche, Ancona, Italy
      *Institute of Infectious Diseases and Public Health and ¶Institute of Pathology, Università Politecnica delle Marche, Ancona, Italy
      †Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA–IRCCS, Ancona, Italy
      ‡Molteni Therapeutics, Siena, Italy
      §Histology, Department of Molecular Pathology and Innovative Therapies, Università Politecnica delle Marche, Ancona, Italy
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  • Funding sources
    This work was supported by Molteni Therapeutics.

  • Conflicts of interest
    C.A., L. F. and G.R. are consultants to the company Molteni Therapeutics who licensed RLP068/Cl patents.

  • O.S. and O.C. contributed equally to this work.

Oriana Simonetti.
E-mail: o.simonetti@univpm.it

Summary

Background  Chronic leg ulceration is a common health problem. It is well known that a clinically relevant bacterial load in chronic cutaneous wounds interferes significantly with the normal process of healing. Staphylococcus aureus is the most important representative of the staphylococcal group which causes clinically relevant infections within immunocompetent patients.

Objectives  To investigate the efficacy of a single treatment of antimicrobial photodynamic therapy (APDT) with RLP068/Cl in a mouse model of a surgical wound infection induced with a methicillin-resistant strain of S. aureus (MRSA).

Methods  Wounds, established through the panniculus carnosus of BALB/c and CD1 mice, were inoculated with 5 × 107 c.f.u. of MRSA. Mice were randomized into four groups respectively receiving no treatment, APDT with placebo, APDT with a new phthalocyanine derivative (RLP068/Cl) and intraperitoneal teicoplanin.

Results  On day 2 from infection, a strong reduction of bacterial counts (≈ 3 logs) was observed in mice treated with RLP068/Cl in comparison with infected untreated mice. On day 9 from infection, a comparable and significant (≈ 2 logs) reduction of bacterial counts was found in mice treated with RLP068/Cl or with teicoplanin. At this time, histological examinations revealed that wounds treated with RLP068/Cl showed a complete re-epithelialization with a continuous epithelial lining.

Conclusions  The results of the in vivo study demonstrated that APDT with RLP068/Cl may be useful in the management of chronic infected wounds, accelerating the repair process through a significant bacterial inhibition.

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