Toxicological evaluation in vitro of novel photosensitizers intended for photodynamic therapy

Area of Science:

• Photodynamic Therapy
• Toxicology
• Biomedical Applications

Background:

• Photosensitizers (PS) are crucial for photodynamic therapy (PDT).
• Preclinical safety assessment of PS requires reliable non-animal testing methods.
• Evaluating skin irritation, phototoxicity, and sensitization is vital for PS development.

Purpose of the Study:

• To assess the safety of three photosensitizers (ZnPcS2, TMPyP, PPIX) using non-animal methods.
• To adapt OECD Test Guidelines (TG) for photosensitizer-specific safety evaluations.
• To determine the potential for skin irritation, phototoxicity, and sensitization of selected PS.

Main Methods:

• Utilized reconstructed human epidermis (RhE) models.
• Adapted OECD TG 439 and 498 for phototoxicity assessment.
• Employed OECD TG 442C and 442D for skin sensitization evaluation.

Main Results:

• TMPyP and PPIX exhibited no skin irritation, phototoxicity, or sensitization.
• ZnPcS2 induced phototoxicity at higher concentrations (50-100 μM) in RhE models.
• ZnPcS2 did not cause skin irritation or sensitization, despite phototoxic effects.

Conclusions:

• Non-animal test methods, adapted from OECD TGs, are suitable for PS safety assessment.
• ZnPcS2, TMPyP, and PPIX demonstrate acceptable safety profiles for PDT applications.
• These findings support the continued development of PS for biomedical applications.