Institute for Materials Chemistry and Engineering, Kyushu University, 744 Nishi-ku, Motooka, Fukuoka 819-0395, Japan.
J Control Release. 2013 May 10;167(3):315-21. doi: 10.1016/j.jconrel.2013.02.016. Epub 2013 Feb 26.
Photofrin® (porfimer sodium) is a photosensitive reagent used for photodynamic therapy (PDT) of tumors and dysplasias. Because only photo-irradiated sites are damaged, PDT is less invasive than systemic treatments. However, a photosensitive reaction is a major side effect of systemically delivered Photofrin. To enhance localization of Photofrin to tumors, we have formulated Photofrin with the tumor-localizing graft copolymer poly(ethylene glycol)-grafted poly(l-lysine), PLL-g-PEG. We demonstrate that Photofrin preferentially interacts with PLL-g-PEG through both ionic and hydrophobic interactions. The serum competitive study showed that the highly PEG-grafted PLL is better for preventing serum binding to the Photofrin/PLL-g-PEG complex. In tumor-bearing mice, formulation of Photofrin with PLL-g-PEG enhanced tumor localization of Photofrin as twice as Photofrin alone and concomitantly suppressed the photosensitivity reaction drastically.
血卟啉单甲醚（血卟啉钠）是一种光敏感试剂，用于肿瘤和发育异常的光动力疗法（PDT）。由于只有光照射的部位受到损伤，因此 PDT 比全身治疗的侵入性更小。然而，光敏反应是全身给予血卟啉单甲醚的主要副作用。为了增强血卟啉单甲醚对肿瘤的定位，我们已经用肿瘤定位接枝共聚物聚乙二醇接枝聚赖氨酸（PLL-g-PEG）对其进行了制剂。我们证明，血卟啉单甲醚通过离子和疏水相互作用优先与 PLL-g-PEG 相互作用。血清竞争研究表明，高度 PEG 接枝的 PLL 更有利于防止血清与血卟啉单甲醚/PLL-g-PEG 复合物结合。在荷瘤小鼠中，用 PLL-g-PEG 对血卟啉单甲醚进行制剂处理可使血卟啉单甲醚在肿瘤中的定位增加一倍，同时大大抑制了光敏反应。
