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.

Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts

“…In contrast, pegylated mTHPC revealed significantly higher concentrations compared to mTHPC in liver, spleen, heart and lung tissue at this time point. Our results suggest a difference in biodistribution of the two substances similar to that observed with pegylated and non-pegylated phthalocyanines (AllŽmann et al, 1995).…”

“…So far pegylation has mainly been applied to high molecular-weight substances such as proteins, enzymes and liposomes, but the pharmaceutical benefits may possibly be conferred upon other compounds. Other studies have shown that the uptake of pegylated phthalocyanine sensitizers in animal tumours is enhanced with increased tumour-to-skin uptake ratios compared to the nonpegylated compound (AllŽmann et al, 1995).…”

Synthesis, characterisation and biocompatibility of surface-functionalised gold nanoparticles

“…The Kupffer cells were identified by their active phagocytic surface morphology and by their location within the sinusoids. AuNPs were found to be accumulated in tumour-infected areas other than the normal tissues and our results are in accordance with the reports of Allemann et al [45]. …”

Hexadecafluorinated zinc phthalocyanine: photodynamic properties against the EMT-6 tumour in mice and pharmacokinetics using 65Zn as a radiotracer

“…Thus in addition to CRM, we recently showed that ZnPcF,6 can readily be formulated in biode- gradable polyethylene glycol-coated poly(lactic acid) nanoparticles (PEG-coated PLA NP), resulting in advantageous biodistribution and excretion pattern for PDT applications (Allemann et al, 1995). Topical application of ZnPcF16 formulated in CRM also induced a good tumour response in the EMT-6 tumour model, whereas ZnPc was inactive under these conditions (Margaron et al, 1992).…”