Factors Influencing in Vivo Disposition of Polymeric Micelles on Multiple Administrations

摘要

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) (A3B-type) was prepared. The A3B-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 ABand A3B-type lactosomes, with variation of conditions, revealed that the high local density of poly(sarcosine) chains of the A3B-type lactosome should relate to the prevention of a polymeric micelle from interacting B-cell receptors.