zn(ii)-phthalocyanine and Carcinoma--Ehrlich-Tumor

Nanoparticles formulated from the biodegradable copolymer poly(lactic-coglycolic acid) (PLGA) were investigated as a drug delivery system to enhance tissue uptake, permeation, and targeting of zinc(II) phthalocyanine (ZnPc) for photodynamic therapy. Three ZnPc nanoparticle formulations were prepared using a solvent emulsion evaporation method and the influence of sonication time on nanoparticle shape, encapsulation and size distribution, in vitro release, and in vivo photodynamic efficiency in tumor-bearing mice were studied. Sonication time did not affect the process yield or encapsulation efficiency, but did affect significantly the particle size. Sonication for 20 min reduced the mean particle size to 374.3 nm and the in vitro release studies demonstrated a controlled release profile of ZnPc. Tumor-bearing mice injected with ZnPc nanoparticles exhibited significantly smaller mean tumor volume, increased tumor growth delay and longer survival compared with the control group and the group injected with free ZnPc during the time course of the experiment. Histopathological examination of tumor from animals treated with PLGA ZnPc showed regression of tumor cells, in contrast to those obtained from animals treated with free ZnPc. The results indicate that ZnPc encapsulated in PLGA nanoparticles is a successful delivery system for improving photodynamic activity in the target tissue.

Topics: Animals; Biocompatible Materials; Carcinoma, Ehrlich Tumor; Drug Delivery Systems; Female; Indoles; Isoindoles; Lactic Acid; Mice; Microscopy, Electron, Scanning; Nanocapsules; Organometallic Compounds; Particle Size; Photochemotherapy; Photosensitizing Agents; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Zinc Compounds

CGP55847, liposomal zinc(II)-phthalocyanine (Zn-Pc), was administered by the intravenous route to Swiss mice bearing intramuscularly implanted Ehrlich carcinomas or to C57/BL6 mice bearing subcutaneously implanted B16 melanomas. Tumors were removed 3 h or 24 h after dosing the intratumoral distribution determined by fluorescence microscopy. Localization of the photosensitizer occurred more rapidly in the Ehrlich carcinoma than in the B16 melanoma; this difference in photosensitizer uptake may be related to a higher degree of vascularization of the carcinoma. The photosensitizer was found in association with blood vessels at 3 h but not 24 h after dosing and appeared to have a greater affinity for areas of tissue necrosis within the tumor compared to viable tumor tissue. Little or no Zn-Pc was detected in the muscle tissue invaded by the Ehrlich carcinoma and was associated with the membranes and the cytosol, but not the nucleus, of cells in both tumors.

Topics: Animals; Carcinoma, Ehrlich Tumor; Drug Carriers; False Positive Reactions; Indoles; Injections, Intravenous; Isoindoles; Liposomes; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Muscle, Skeletal; Necrosis; Organometallic Compounds; Photosensitizing Agents; Tissue Distribution; Zinc; Zinc Compounds