Initial Evaluation of Tumor Accumulation during Multiple Dosing of <sup>125</sup>I-labeled Linear-polyglycerol-modified Lactosome

Lactosome is a polymeric micelle composed of an amphiphilic polydepsipeptide, a hydrophilic block poly(sarcosine)70, and a hydrophobic block poly(L-lactic acid)30(PSar70-block-PLLA30), which accumulates in solid tumors through the enhanced permeability and retention effect. However, following administration its pharmacokinetics shift from tumor accumulation to liver sequestration due to anti-lactosome IgM production triggered by the initial administration. This phenomenon is called Accelerated Blood Clearance. To enhance tumor accumulation after multiple doses, a novel nanoparticle composed of lactosome modified with linear-poly(glycerol)10 (lin-PG10) (lin-PG10 lactosome) was prepared. Amphiphilic polymer with lin-PG10 and PLLA30 were synthesized and modified into lactosome by the Film method. IgM production of lin-PG10 lactosome was evaluated by ELISA using mice plasma collected 7 days after dosing. 125I-labeled 10%lin-PG10 lactosome was prepared by incorporating N-[125I]iodobenzoyl poly(L-lactic acid)30(125I-BzPLLA30). Biodistribution was compared 1st and 2nd doses using Colon-26 bearing mice. 10%lin-PG10 lactosome was reduced anti-lactosome IgM production compared with lactosome. Evaluation of biodistribution in Colon-26 bearing mice showed that the 1st dose showed accumulation in tumors, but the 2nd dose showed a reduction in the amount of accumulation in tumors, which was not sufficient improvement. This suggests that antibody production may be inhibited by introducing functional groups into lactosomes, although there is room for improvement.