Rat reproductive performance following photodynamic therapy with topically administered Photofrin

A rat animal model was used for comparing the photodynamic efficacy of two formulations of topically administered Photofrin in the uterus: 0.7 mg/kg Photofrin and 0.7 mg/kg Photofrin + 4% Azone, a penetration-enhancing agent. Uterine structure and reproductive performance were evaluated following illumination with 80 J/cm2 of 630 nm light. Fluorescence microscopy was employed to determine drug localization in frozen uterine sections at various times after drug administration. Functionality studies demonstrated a significant reduction in the number of implantations per treated uterine horn compared to controls. The mean number of implantations decreased systematically on increasing the interval between Photofrin administration and light application. At 72 h, 0.88 +/- 0.52 gestational sacs per rat were recorded with Photofrin therapy, compared with 8.1 +/- 1.12 (P = 0.01) on the untreated side, indicating nearly complete loss of reproductive capability. Similar results were achieved after only 3 h treatment with Photofrin + Azone (0.38 +/- 0.26 sacs per rat versus 7.5 +/- 1.07 on the untreated side; P = 0.01). This indicates that the effect of Photofrin can be enhanced either by extending the drug incubation period from 3 to 72 h or by adding the penetration-enhancing drug Azone. Fluorescence pharmacokinetic studies suggest that both forms of topically administered Photofrin are diffusely distributed throughout the endometrium at virtually the same rate. However, Azone may enhance the selectivity of photodynamic therapy by facilitating drug targeting to critical endometrial structures.