Enhanced photodynamic activity of meso-tetra(4-hydroxyphenyl)porphyrin by incorporation into sub-200 nm nanoparticles

A photosensitizer, meso-tetra(hydroxyphenyl)porphyrin (p-THPP) was incorporated into sterile submicronic nanoparticles of poly(D,L-lactide-co-glycolide) (50:50 and 75:25 PLGA) and poly(D,L-lactide) (PLA). With all polymers used, sub-130 nm p-THPP-loaded nanoparticles with similar drug loadings and entrapment efficiencies were produced using the emulsification-diffusion technique. The photodynamic activity (photocytotoxicity) of these nanoparticles was evaluated on EMT-6 mammary tumour cells in comparison with the free drug. The influence of drug concentration (3-10 mug/ml), incubation time (5-60 min) and light dose (6-9 J/cm(2)) on p-THPP photocytotoxic efficiency was investigated. With all p-THPP formulations tested, cell viability decreased with increasing values of these parameters. The beneficial effect of nanoencapsulation compared to free drug was highlighted at drug concentrations up to 6 mug/ml and short incubation times (15-30 min). The most important photocytotoxicity was observed with 50:50 PLGA nanoparticles allowing low drug doses and short drug administration-irradiation intervals for local photodynamic therapy. (C) 2003 Elsevier Science B.V. All rights reserved.