Wowra B, Mentrup E, Zeller W J, Stricker H, Sturm V
Projekt Neuroonkologie des Tumorzentrums Heidelberg/Mannheim.
Onkologie. 1988 Apr;11(2):81-4. doi: 10.1159/000216493.
CT follow-up studies of liposome-entrapped metrizamide after intraneoplastic injection into neurogenic s.c. rat tumors were performed. By closely resembling clinical examination conditions, the experimental design has proven suitable in determining the in vivo kinetics of these interstitial liposome deposits. When compared to free metrizamide which may be considered an analogue of water-soluble chemotherapeutics, the encapsulation of metrizamide in liposomes resulted in a retarded decline of the contrast enhancement. Diffusion of liposomes could not be detected and the X-ray attenuation values measured within the liposome deposits continuously decreased with time for both types of liposomes. In the case of multilamellar vesicles, this significantly corresponded to a zero order kinetics with a mean halflife of 300 h. An initial increment in the X-ray attenuation of the liposome deposits might be due to the interstitial absorption of the water component of the liposome-dispersion. Because of the pronounced retardation effect of multilamellar liposomes resulting in a 140-fold prolongation of the interstitial retention time of metrizamide and due to their release kinetics these vesicles may be an appropriate carrier system for a local interstitial chemotherapy modality. Small unilamellar vesicles having an interstitial half-life of 14 h may be used as a faster component of a composed therapy system.
对大鼠神经源性皮下肿瘤进行瘤内注射脂质体包裹的甲泛葡胺后的CT随访研究。通过紧密模拟临床检查条件,该实验设计已证明适用于确定这些间质脂质体沉积物的体内动力学。与可被视为水溶性化疗药物类似物的游离甲泛葡胺相比,甲泛葡胺包裹在脂质体中导致对比增强的下降延迟。未检测到脂质体的扩散,并且两种类型的脂质体在脂质体沉积物内测量的X射线衰减值均随时间持续下降。对于多层囊泡,这显著符合零级动力学,平均半衰期为300小时。脂质体沉积物的X射线衰减的初始增加可能是由于脂质体分散体中水成分的间质吸收。由于多层脂质体的显著延迟效应导致甲泛葡胺的间质保留时间延长140倍,并且由于它们的释放动力学,这些囊泡可能是局部间质化疗方式的合适载体系统。具有14小时间质半衰期的小单层囊泡可作为复合治疗系统中较快的成分使用。