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.

• Authors: E Allémann, N Brasseur, O Benrezzak, J Rousseau, S V Kudrevich, R W Boyle, J C Leroux, R Gurny, J E Van Lier
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 47 Issue 5 Pg. 382-7 (May 1995) ISSN: 0022-3573 [Print] England
• PMID: 7494187 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Colloids
• Delayed-Action Preparations
• Emulsions
• Indoles
• Lactates
• Organometallic Compounds
• Polyesters
• Polymers
• Radiation-Sensitizing Agents
• Solvents
• hexadecafluoro zinc phthalocyanine
• Lactic Acid
• Polyethylene Glycols
• poly(lactide)
• cremophor EL
• Glycerol

Topics

• Animals
• Colloids
• Delayed-Action Preparations
• Emulsions
• Glycerol (analogs & derivatives)
• Indoles (administration & dosage, pharmacology)
• Injections, Intravenous
• Lactates
• Lactic Acid
• Male
• Mammary Neoplasms, Experimental (drug therapy, metabolism)
• Mice
• Mice, Inbred BALB C
• Microspheres
• Organometallic Compounds (administration & dosage, pharmacology)
• Photochemotherapy
• Polyesters
• Polyethylene Glycols
• Polymers
• Radiation-Sensitizing Agents (administration & dosage, pharmacokinetics)
• Solvents
• Tissue Distribution