Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan; Center for Drug Delivery Research, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan; Center for Physical Pharmaceutics, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan.
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan.
Colloids Surf B Biointerfaces. 2017 Nov 1;159:360-365. doi: 10.1016/j.colsurfb.2017.08.002. Epub 2017 Aug 4.
Poly(DL-lactide-co-glycolide) (PLGA) has been widely used and studied because of its biocompatibility and biodegradability. Recently, the usefulness of nanoparticles using poly(L-lactide-co-glycolide) (PLLGA) having a higher glass transition temperature than PLGA was suggested. In this study, we investigated the availability of boron compound-loaded PLGA and PLLGA nanoparticles for boron neutron capture therapy (BNCT) by conducting biodistribution study using tumor-bearing mice. o-Carborane, a hydrophobic boron compound, was used as a boron carrier, and o-carborane-albumin conjugate was used as a control. We prepared PLGA and PLLGA nanoparticles with diameters of 100nm and 150nm. In 100-nm PLLGA nanoparticles, the boron concentration in the tumor reached 113.9±15.8μg/g of tissue at 8h after administration. This result indicated that 100-nm PLLGA nanoparticles were able to achieve an intratumoral B concentration of 20μg/g without replacing the B with B. In addition, by nanoparticulation using PLGA7510 and PLLGA7510, intratumoral boron concentration was 1.7-3.2 and 3.5-4.2 times higher than that of the o-carborane-albumin conjugate, respectively. The tumor/blood ratios of boron concentration reached over 5 at 8-12h after injection. Boron atoms in nanoparticles were excreted mainly in the urine, and characteristic accumulation was not observed in other organs. These results suggested that 100-nm PLLGA nanoparticles were particularly useful for BNCT.
聚（DL-丙交酯-co-乙交酯）（PLGA）因其生物相容性和可生物降解性而被广泛研究和应用。最近，有人提出使用玻璃化转变温度高于 PLGA 的聚（L-丙交酯-co-乙交酯）（PLLGA）纳米粒子的有用性。在这项研究中，我们通过使用荷瘤小鼠进行生物分布研究，研究了载硼 PLGA 和 PLLGA 纳米粒子在硼中子俘获治疗（BNCT）中的可用性。o-卡硼烷是一种疏水性硼化合物，用作硼载体，o-卡硼烷-白蛋白缀合物用作对照。我们制备了直径为 100nm 和 150nm 的 PLGA 和 PLLGA 纳米粒子。在 100nm 的 PLLGA 纳米粒子中，给药后 8 小时肿瘤中的硼浓度达到 113.9±15.8μg/g 组织。这一结果表明，100nm 的 PLLGA 纳米粒子能够在不替代硼的情况下达到 20μg/g 的肿瘤内硼浓度。此外，通过使用 PLGA7510 和 PLLGA7510 进行纳米粒化，肿瘤内的硼浓度分别比 o-卡硼烷-白蛋白缀合物高 1.7-3.2 和 3.5-4.2 倍。注射后 8-12 小时，肿瘤/血液中硼浓度比值超过 5。纳米粒子中的硼原子主要通过尿液排出，未观察到其他器官有特征性蓄积。这些结果表明，100nm 的 PLLGA 纳米粒子特别适用于 BNCT。
