Protoporphyrin IX (PpIX) loaded PLGA nanoparticles for topical Photodynamic Therapy of melanoma cells

Abstract

Introduction: Nanoparticles (Np) can increase drug efficacy and overcome problems associated with solubility and aggregation in a solution of PpIX.

Purpose: Evaluate if Np interferes in the photophysical and photobiological capacity of the PpIX comparing with free PpIX intended for topical PDT of melanoma.

Methods: In vitro photophysical evaluation of Np-PpIX was carried out through singlet oxygen (₁O²) quantum yield. In vitro cytotoxicity and phototoxicity assays have used murine melanoma cell culture.

Results: The quantum yield of singlet oxygen has shown that Np did not influence the formation capacity of this reactive species. In the dark, all PpIX-Nps concentrations were less cytotoxic compared to free drugs. At a higher light dose (1500 mJ.cm²) 3.91 μg / mL PpIX had similar % viable cells for free and Np (∼34 %) meaning Nps did not interfere in the photodynamic effect of PpIX. However, at 7.91 μg / mL the phototoxicity increased for both (5.8 % viable cells for free versus 21.7 % for Nps). Despite the higher phototoxicity of free PpIX at this concentration, greater cytotoxicity in the dark was obtained (∼49 % viable cells for free versus ∼90.6 % Np) which means Nps protect the tumor tissue from the photodynamic action of PpIX.

Conclusions: Np is a potential delivery system for melanoma skin cancer, since it maintained the photophysical properties of PpIX and excellent in vitro phototoxicity effect against melanoma cells, reducing cell viability ∼80 % (7.91 μg / mL PpIX in Nps) and provides safe PDT (due to lower cytotoxicity in the dark).

Keywords: Cytotoxicity; Nanoparticles; PDT; Phototoxicity; Protoporphyrin IX; Skin cancer.