Bucking M, Gudgin Dickson E F, Farahani M, Fischer F, Holmes D, Jori G, Kennedy J C, Kenney M E, Peng X, Pottier R H, Weagle G
Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, ON.
J Photochem Photobiol B. 2000 Nov;58(2-3):87-93. doi: 10.1016/s1011-1344(00)00108-1.
Palladium octabutoxynaphthalocyanine (PdNc(OBu)8) is a potential photothermal therapy (PTT) agent, absorbing strongly in the near-infrared region with no ability to induce photodynamic-type sensitisation (unlike many related napthalocyanines). We report here on the application of high pressure liquid chromatography (HPLC) with near-infrared absorption detection for the determination of the tissue accumulation and clearance of PdNc(OBu)8 in a tumour-bearing mouse model (Balb/c mice with EMT6 carcinoma tumour). Due to its insolubility in aqueous-based solvents, the drug was delivered intraperitoneally in a Cremophor-containing vehicle. Good selective accumulation of the drug into the tumour versus muscle or skin is observed, with the best combination of selectivity and tumour concentration occurring at 24-72 h after drug administration. Clearance times are quite long. Comparison with other similar drugs as reported in the literature indicates that the Cremophor-containing vehicle is likely in large part responsible for the observed pharmacokinetic behaviour. This drug shows potential for PTT and will be investigated further for therapy in this animal model.
八丁氧基萘酞菁钯(PdNc(OBu)8)是一种潜在的光热疗法(PTT)药物,在近红外区域有强烈吸收,且无诱导光动力型敏化的能力(与许多相关萘酞菁不同)。我们在此报告采用带近红外吸收检测的高压液相色谱法(HPLC)来测定PdNc(OBu)8在荷瘤小鼠模型(患有EMT6癌瘤的Balb/c小鼠)中的组织蓄积和清除情况。由于该药物在水基溶剂中不溶,因此通过含聚氧乙烯蓖麻油的载体经腹腔给药。观察到该药物相对于肌肉或皮肤对肿瘤有良好的选择性蓄积,给药后24 - 72小时出现选择性和肿瘤浓度的最佳组合。清除时间相当长。与文献中报道的其他类似药物比较表明,含聚氧乙烯蓖麻油的载体很可能在很大程度上导致了所观察到的药代动力学行为。这种药物显示出光热疗法的潜力,并将在该动物模型中进一步研究其治疗效果。