Lipid-associated methylpheophorbide-a (hexyl-ether) as a photodynamic agent in tumor-bearing mice.
Lipid-associated methylpheophorbide-a (hexyl-ether) as a photodynamic agent in tumor-bearing mice.
复制标题
脂质相关的甲基脱镁叶绿酸-a（己基醚）作为荷瘤小鼠的光动力剂。
DOI：
10.1111/j.1751-1097.1993.tb04982.x
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发表时间：
1993
影响因子：
3.3
通讯作者：
Henderson,BW
中科院分区：
文献类型：
--
作者：
Mayhew,E;Vaughan,L;Panus,A;Murray,M;Henderson,BW
脂质体是一种更有选择性地将光敏剂（PS）递送至肿瘤的潜在系统。脱镁叶绿酸是一系列正在研究用于光动力疗法的新型 PS。在小鼠中测定了甲基脱镁叶绿酸-a-（己基醚）（MPH）与由高和低转变温度脂质组成的带负电荷磷脂囊泡相关的药代动力学、抗肿瘤反应和正常组织效应。在一些制剂中还包括单唾液酸神经节苷脂，已知它可以赋予脂质体较长的循环时间。通常，对于大多数脂质体组合物，水不溶性 MPH 可以定量掺入多层脂质体中，含量高达至少 20 mol MPH/mol 脂质%，并超声处理形成透明悬浮液。来自电子显微镜和水性空间标记物包埋的证据表明，超声处理形成的颗粒不是标准脂质体。与溶解在吐温 80 中的 MPH 相比，MPH (0.4 μmol/kg) 给药 24 小时后，脂质相关的 MPH 对光治疗（135 J/cm2、665 nm 氩染料激光）的抗肿瘤反应稍大但显着更高 (P <0.05)。MPH 的脂质或吐温 80 制剂之间的肿瘤摄取和肿瘤细胞光敏化没有重大差异，而依赖于脂质MPH 给药后的成分和时间，脂质制剂导致闭塞性血管损伤所需的光剂量增加。药代动力学研究表明脂质和 MPH 在体内快速解离。脂质制剂可用于溶解 MPH，并可改善该 PS 的治疗效果。
Liposomes are a potential system for more selective delivery of photosensitizers (PS) to tumors. Pheo‐phorbides are one series of new PS under investigation for use in photodynamic therapy. The pharmacokinetics, anti‐tumor response and normal tissue effects of methylpheophorbide‐a‐(hexyl‐ether) (MPH) associated with negatively charged phospholipid vesicles composed of high and low transition temperature lipids were determined in mice. In some preparations monosialoganglioside, which is known to impart long circulation time to liposomes was also included. Normally water‐insoluble MPH could be quantitatively incorporated in multilamellar liposomes up to at least 20 mol MPH/mol lipid% for most liposome compositions and sonicated to form clear suspensions. Evidence from electron microscopy and entrapment of aqueous space markers indicated that the particles formed by sonication were not standard liposomes. Anti‐tumor responses to light treatment (135 J/cm2, 665 nm argon‐dye laser) 24 h after MPH (0.4 μmol/kg) administration were slightly but significantly greater (P <0.05) for lipid associated MPH compared to MPH solubilized in Tween 80. There were no major differences in tumor uptake and tumor cell photosensitization between lipid or Tween 80 formulations of MPH, whereas, dependent on lipid composition and time after MPH administration, the doses of light required to cause occlusive vascular damage were increased for the lipid formulations. Pharmacokinetic studies showed rapid dissociation between lipids and MPHin vivo. Lipid formulations are useful for solubilizing MPH and may improve the therapeutic effects of this PS.