title: PEG-coated poly(lactic acid) nanoparticles for the delivery of hexadecafluoro zinc phthalocyanine to EMT-6 mouse mammary tumours.
abstract: Hexadecafluoro zinc phthalocyanine (ZnPcF16), a second generation sensitizer for the photodynamic therapy of cancer, was incorporated in three vehicles: poly(D,L-lactic acid) (PLA) nanoparticles, polyethylene glycol (PEG)-coated nanoparticles and a Cremophor EL (CRM) oil-water emulsion. Nanoparticles were prepared by the salting-out procedure. Biodistribution of the dye was assessed by fluorescence in EMT-6 mammary tumour bearing mice after intravenous injection of 1 mumol kg-1 ZnPcF16. Plain nanoparticles were rapidly retained by the reticuloendothelial system (RES) as reflected by the low area under the blood concentration-time curve (AUC0-168, 57 micrograms h g-1). Little tumour uptake of the dye was observed with this formulation. In contrast, PEG-coated nanoparticles displayed a reduced RES uptake, leading to significantly higher blood levels over an extended period (t1/2 30 h; AUC 0-168 227 micrograms h g-1) and enhanced tumour uptake. At 48 h post injection, tumour to skin and tumour to muscle concentration ratios reached 3.5 and 10.8, respectively. Blood levels of ZnPcF16 after administration as a CRM emulsion decreased faster than with PEG-coated nanoparticles (t1/2 12 h), but since no early liver uptake was observed, the AUC0-168 and the tumour uptake were only slightly lower. However, with the CRM formulation, a late liver uptake was observed, reaching 51% of the injected dose after 7 days.
mesh_terms: D000818:Animals; D003102:Colloids; D003692:Delayed-Action Preparations; D004655:Emulsions; D005990:Glycerol / Q000031:analogs & derivatives; D007211:Indoles / Q000008:administration & dosage* / Q000494:pharmacology; D007275:Injections, Intravenous; D007773:Lactates; D019344:Lactic Acid; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D010778:Photochemotherapy; D011091:Polyesters; D011092:Polyethylene Glycols; D011108:Polymers; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012997:Solvents; D014018:Tissue Distribution
chemical_list: D003102:Colloids; D003692:Delayed-Action Preparations; D004655:Emulsions; D007211:Indoles; D007773:Lactates; D009942:Organometallic Compounds; D011091:Polyesters; D011108:Polymers; D011838:Radiation-Sensitizing Agents; D012997:Solvents; C097030:hexadecafluoro zinc phthalocyanine; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); C000515:cremophor EL; D005990:Glycerol