Factors Influencing in Vivo Disposition of Polymeric Micelles on Multiple Administrations
Factors Influencing in Vivo Disposition of Polymeric Micelles on Multiple Administrations
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DOI：
10.1021/ml500112u
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发表时间：
2014-08-01
影响因子：
4.2
通讯作者：
Kimura, Shunsaku
中科院分区：
文献类型：
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作者：
Hara, Eri;Ueda, Motoki;Kimura, Shunsaku
乳小体是由两亲性多肽、聚（肌氨酸）(64)-块聚（l -乳酸）（30）（ab型）组成的聚合胶束，通过增强渗透性和滞留性（EPR）作用在实体瘤中积累。然而，乳小体在多次给药后，由于抗乳小体IgM的产生，其药代动力学从肿瘤积累到肝脏，这是由第一次给药触发的。这种现象被称为加速血液清除（ABC）。为了减少抗乳小体IgM的产生，制备了一种由聚（肌氨酸）（23）(3)-嵌段聚（l -乳酸）（30）（a (3) b型）组成的新型纳米颗粒。在第二次给药时，由于抑制抗体产生，A(3) b型乳小体在体内的分布与第一次给药时相似。这项涉及AB-和A(3) b型乳小体的研究，在不同的条件下，揭示了A(3) b型乳小体的高局部多肌氨酸链密度可能与防止聚合物胶束与b细胞受体相互作用有关。
Lactosome is a polymeric micelle composed of amphiphilic polydepsipeptide, poly(sarcosine)(64)-block-poly(L-lactic acid)(30) (AB-type), which accumulates in solid tumors through the enhanced permeability and retention (EPR) effect. However, lactosome on multiple administrations changed its pharmacokinetics from accumulation in tumors to liver due to the production of antilactosome IgM, which was triggered by the first administration. This phenomenon is called the accelerated blood clearance (ABC). In order to reduce the production of antilactosome IgM, a novel nanoparticle composed of (poly(sarcosine)(23))(3)-block-poly(L-lactic acid)(30) (A(3)B-type) was prepared. The A(3)B-type lactosome at the second administration showed an in vivo disposition similar to that at the first administration due to suppression of antibody production. This study involving the AB- and A(3)B-type lactosomes, with variation of conditions, revealed that the high local density of poly(sarcosine) chains of the A(3)B-type lactosome should relate to the prevention of a polymeric micelle from interacting B-cell receptors.