Allémann E, Brasseur N, Benrezzak O, Rousseau J, Kudrevich S V, Boyle R W, Leroux J C, Gurny R, Van Lier J E
MRC Group in the Radiation Sciences, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
J Pharm Pharmacol. 1995 May;47(5):382-7. doi: 10.1111/j.2042-7158.1995.tb05815.x.
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.
十六氟锌酞菁（ZnPcF16）是一种用于癌症光动力治疗的第二代敏化剂，被载入三种载体中：聚（D，L-乳酸）（PLA）纳米颗粒、聚乙二醇（PEG）包被的纳米颗粒和聚氧乙烯蓖麻油（CRM）油水乳液。纳米颗粒通过盐析法制备。在给荷EMT-6乳腺肿瘤的小鼠静脉注射1 μmol kg-1 ZnPcF16后，通过荧光评估染料的生物分布。普通纳米颗粒被网状内皮系统（RES）迅速摄取，这从血药浓度-时间曲线下的低面积（AUC0-168，57 μg h g-1）可以看出。用这种制剂观察到染料在肿瘤中的摄取很少。相比之下，PEG包被的纳米颗粒RES摄取减少，导致在较长时间内血药水平显著更高（t1/2 30 h；AUC 0-168 227 μg h g-1），并且肿瘤摄取增强。注射后48小时，肿瘤与皮肤以及肿瘤与肌肉的浓度比分别达到3.5和10.8。作为CRM乳液给药后，ZnPcF16的血药水平下降速度比PEG包被的纳米颗粒快（t1/2 12 h），但由于未观察到早期肝脏摄取，AUC0-168和肿瘤摄取仅略低。然而，对于CRM制剂，观察到晚期肝脏摄取，7天后达到注射剂量的51%。
