Tabata Y, Murakami Y, Ikada Y
Research Center for Biomedical Engineering, Kyoto University, Japan.
J Control Release. 1998 Jan 2;50(1-3):123-33. doi: 10.1016/s0168-3659(97)00129-6.
The body distribution and tumor accumulation of polymers were evaluated using poly(vinyl alcohol) (PVA) which has the simplest chemical structure among water-soluble polymers, similar to poly(ethylene glycol). To study the effect of polymer size on the tumor accumulation, we used not only water-soluble PVA with different molecular weights but also PVA microgels prepared through gamma-irradiation of aqueous PVA solutions. The PVA specimens in the aqueous solution were intravenously injected to mice carrying a tumor mass at their footpad. Both types of PVA (water-soluble and microgel) of larger size were retained in the blood circulation for longer time periods and excreted more slowly from the kidney than those of smaller size. The plasma half-life period of PVA became longer with increasing size both for the water-soluble and microgel PVA, indicating that the body fate of PVA is governed only by the size. Both the water-soluble PVA and PVA microgels were accumulated in tumor tissue to a significantly greater extent than in normal tissue. The size dependence of the plasma half-life period and tumor accumulation was similar between the water-soluble PVA and the PVA microgels and the tumor accumulation became maximum around the size of 60 nm both for water-soluble and microgel PVA. A pharmacokinetical study demonstrated that the tumor uptake rate index of PVA decreased with the increase in PVA size. On the other hand, the greater the size, the larger the value of the area under the blood concentration-time curve (AUC). In addition, the PVA around 60 nm in diameter showed the smallest liver clearance. It was concluded that the balance between the uptake rate and the AUC as well as the liver clearance resulted in the maximum accumulation of PVA with the size of 60 nm.
使用聚乙烯醇（PVA）评估聚合物的体内分布和肿瘤蓄积情况，PVA在水溶性聚合物中具有最简单的化学结构，与聚乙二醇类似。为了研究聚合物尺寸对肿瘤蓄积的影响，我们不仅使用了不同分子量的水溶性PVA，还使用了通过对PVA水溶液进行γ射线辐照制备的PVA微凝胶。将水溶液中的PVA标本静脉注射到脚垫处带有肿瘤块的小鼠体内。与较小尺寸的PVA相比，两种较大尺寸的PVA（水溶性和微凝胶）在血液循环中的保留时间更长，从肾脏排泄得更慢。水溶性和微凝胶PVA的血浆半衰期均随着尺寸的增加而延长，这表明PVA在体内的命运仅由尺寸决定。水溶性PVA和PVA微凝胶在肿瘤组织中的蓄积程度均明显高于正常组织。水溶性PVA和PVA微凝胶之间血浆半衰期和肿瘤蓄积的尺寸依赖性相似，水溶性和微凝胶PVA在尺寸约为60 nm时肿瘤蓄积达到最大值。一项药代动力学研究表明，PVA的肿瘤摄取率指数随PVA尺寸的增加而降低。另一方面，尺寸越大，血药浓度-时间曲线下面积（AUC）的值越大。此外，直径约60 nm的PVA肝脏清除率最小。得出的结论是，摄取率与AUC以及肝脏清除率之间的平衡导致尺寸为60 nm的PVA蓄积量最大。
