New method for delivering a hydrophobic drug for photodynamic therapy using pure nanocrystal form of the drug
New method for delivering a hydrophobic drug for photodynamic therapy using pure nanocrystal form of the drug
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DOI：
10.1021/mp060117f
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发表时间：
2007-03-01
影响因子：
4.9
通讯作者：
Prasad, Paras N.
中科院分区：
文献类型：
--
作者：
Baba, Koichi;Pudavar, Haridas E.;Prasad, Paras N.
提出了一种使用纳米晶体（纳米尺寸晶体）以纯形式递送疏水性药物的无载体方法。为了证明这项技术，使用再沉淀法合成了疏水性光敏抗癌药物 2-devinyl-2-(1-hexyloxyethy)pyropheophorbide (HPPH) 的纳米晶体。所得药物纳米晶体在水分散体中是单分散且稳定的，无需额外的稳定剂（表面活性剂）。共聚焦显微镜显示，这些纯药物纳米晶体被癌细胞以高亲和力吸收。尽管药物的荧光和光动力活性在水悬浮液中以纳米晶体的形式基本上被猝灭，但这两个特性在体外和体内条件下都得到了恢复。药物活性和荧光的恢复可能是由于纳米晶体与血清白蛋白的相互作用，导致药物纳米晶体转化为分子形式。这通过在胎牛血清 (FBS) 或牛血清白蛋白 (BSA) 存在下的类似恢复得到证实。在相似的处理条件下，纳米晶体形式或 1% Tween-80/水配方的 HPPH 显示出相当的体外和体内功效。
A carrier-free method for delivery of a hydrophobic drug in its pure form, using nanocrystals (nanosized crystals), is proposed. To demonstrate this technique, nanocrystals of a hydrophobic photosensitizing anticancer drug, 2-devinyl-2-(1-hexyloxyethyl)pyropheophorbide (HPPH), have been synthesized using the reprecipitation method. The resulting drug nanocrystals were monodispersed and stable in aqueous dispersion, without the necessity of an additional stabilizer (surfactant). As shown by confocal microscopy, these pure drug nanocrystals were taken up by the cancer cells with high avidity. Though the fluorescence and photodynamic activity of the drug were substantially quenched in the form of nanocrystals in aqueous suspension, both these characteristics were recovered under in vitro and in vivo conditions. This recovery of drug activity and fluorescence is possibly due to the interaction of nanocrystals with serum albumin, resulting in conversion of the drug nanocrystals into the molecular form. This was confirmed by demonstrating similar recovery in presence of fetal bovine serum (FBS) or bovine serum albumin (BSA). Under similar treatment conditions, the HPPH in nanocrystal form or in 1% Tween-80/water formulation showed comparable in vitro and in vivo efficacy.