Pharmacokinetic, toxicological and phototherapeutic studies

LAURA N. MILLA; EDITH I. YSLAS; ANA CABRAL; EDGARDO N. DURANTINI; SIVIA ROMANINI; VIVIANA RIVAROLA; MABEL BERTUZZI

BIOMEDICINE & PHARMACOTHERAPY = BIOMEDECINE & PHARMACOTHERAPIE.

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Año: 2009 vol. 63 p. 209 - 215

0753-3322

Photodynamic therapy (PDT) is an alternative modality for cancer therapy. It induces neoplasic cells death through photoachievable sensitizers. The aim of this work was to evaluate the pharmacokinetic, toxic and phototherapeutic effects of the phthalocyanine ZnPcCF3 in a Balb/c mice tumor model. Biodistribution studies were carried out by intraperitoneal injection of 0.2 mg/kg ZnPcCF3. Histological studies and serum biochemical parameters were used to evaluate hepatic and renal toxicity and functionality. After tumor irradiation (210 J/cm2), an analysis of tumor necrosis degree was used to evaluate the phototherapeutic effects. It was measured at 1, 2, 3 and 4 days after PDT. Vital staining was performed by intraperitoneal injection of 0.35 ml 1% Evans Blue solution. Six hours later, tumors were excised and examined. The unstained area was attributed to necrotic tissue, whereas the stained area showed tissue with preserved blood supply. ZnPcCF3 was accumulated in spleen, liver and duodenum. It suggests that ZnPcCF3 is eliminated from the body via bileegut. The phthalocyanine was not found in brain, therefore, it would not cross the bloodebrain barrier, thus toxicity risk in the central nervous system is not probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 was not found in brain, therefore, it would not cross the bloodebrain barrier, thus toxicity risk in the central nervous system is not probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 was not found in brain, therefore, it would not cross the bloodebrain barrier, thus toxicity risk in the central nervous system is not probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 was not found in brain, therefore, it would not cross the bloodebrain barrier, thus toxicity risk in the central nervous system is not probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 tumor necrosis degree was used to evaluate the phototherapeutic effects. It was measured at 1, 2, 3 and 4 days after PDT. Vital staining was performed by intraperitoneal injection of 0.35 ml 1% Evans Blue solution. Six hours later, tumors were excised and examined. The unstained area was attributed to necrotic tissue, whereas the stained area showed tissue with preserved blood supply. ZnPcCF3 was accumulated in spleen, liver and duodenum. It suggests that ZnPcCF3 is eliminated from the body via bileegut. The phthalocyanine was not found in brain, therefore, it would not cross the bloodebrain barrier, thus toxicity risk in the central nervous system is not probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 was not found in brain, therefore, it would not cross the bloodebrain barrier, thus toxicity risk in the central nervous system is not probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 was not found in brain, therefore, it would not cross the bloodebrain barrier, thus toxicity risk in the central nervous system is not probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3 probable. Moreover, ZnPcCF3 does not accumulate in skin, it would eliminate cutaneous photosensitizing risks. The dose of 0.2 mg/kg ZnPcCF3