New drug delivery system for water-soluble drugs using silicone and its usefulness for local treatment: application of GCV-silicone to GCV/HSV-tk gene therapy for brain tumor.
New drug delivery system for water-soluble drugs using silicone and its usefulness for local treatment: application of GCV-silicone to GCV/HSV-tk gene therapy for brain tumor.
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DOI：
10.1016/s0168-3659(02)00236-5
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发表时间：
2002-11
期刊：
影响因子：
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通讯作者：
M. Maeda;S. Moriuchi;A. Sano;T. Yoshimine
中科院分区：
文献类型：
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作者：
M. Maeda;S. Moriuchi;A. Sano;T. Yoshimine
研究了水溶性低分子量药物从硅胶中的控释及其作为局部治疗药物的有效性。为了应用更昔洛韦/单纯疱疹病毒胸苷激酶（GCV/HSV-tk）自杀基因治疗脑肿瘤，制备了两种含GCV的硅油制剂进行评价。在体外，GCV从由单一基质组成的基质型制剂中的释放的特征在于Fickian扩散，而覆盖棒型制剂，其中外层的侧表面覆盖有100%硅酮，表现出近零级释放模式。在一项使用大鼠9 L胶质母细胞瘤模型的体内研究中，将GCV-硅胶制剂给予脑肿瘤中，在给药后产生持续4天的脑内GCV浓度，其优异的抗肿瘤作用等于或优于每日腹膜内给予GCV水溶液的抗肿瘤作用，剂量小于腹膜内给药溶液总剂量的1/100。此外，在血液中未检测到GCV，表明脑内给予GCV-硅胶制剂可预期全身不良反应减少。
Controlled release of a water-soluble low-molecular-weight drug from silicone and its usefulness as a local therapeutic drug were studied. For application to ganciclovir/helpes simplex virus thymidine kinase (GCV/HSV-tk) suicide gene therapy for brain tumor, two kinds of GCV-containing silicone formulations were prepared for evaluation. In vitro, GCV release from matrix-type formulation consisting of a single matrix was characterized by Fickian diffusion, while covered-rod-type formulation, in which the side surface of the outer layer was covered with 100% silicone, exhibited a near-zero-order release pattern. In an in vivo study using a rat 9L glioblastoma model, administration of GCV-silicone formulation into brain tumor yielded sustained intracerebral GCV concentration for 4 days after administration, with excellent antitumor effect equal to or better than that of daily intraperitoneal administration of aqueous solution of GCV, at a dose less than 1/100 of the total dose of solution for intraperitoneal administration. Furthermore, GCV was undetectable in blood, suggesting that decrease in systemic adverse reactions can be expected with intracerebral administration of GCV-silicone formulation.