Block copolymers modify the internalization of micelle-incorporated probesinto neural cells

An important therapeutic concern is rate and extent of internalization of d rugs into cells. Hydrophilic agents often internalize poorly and slowly, an d highly lipophilic ones too rapidly. The incorporation of drugs into micel les allows regulation of their internalization parameters, and newly-descri bed block copolymers can be selectively tailored to suit specific drugs. Th is report compares internalization of Cell Tracker CM-DiI (DiI), a highly l ipophilic non-cytotoxic fluorescent probe in common use in biology, from th e freely-presented (non-micelle-incorporated) and micelle-incorporated stat es. DiI was effectively incorporated (> 60%) into 25-50 nm diameter spheric al micelles made from polycaprolactone-b-polyethylene oxide block copolymer . Confocal microscopy was used to evaluate the internalization of DiI into mixed neuron-glia cultures (2-14 days in vitro, 2DIV-14DIV). Incorporation of DiI into micelles strikingly reduced the rate and extent of its internal ization in both 2DIV and 14DIV cultures. Both the age of the cultures and t he block copolymer employed to construct the micelles significantly influen ce the internalization of micelle-incorporated probe. (C) 2001 Elsevier Sci ence B.V. All rights reserved.