Cytotoxicity of a unimolecular polymeric micelle and its degradation products

The cytotoxicity of a unimolecular polymeric micelle (1) and its degradation products was assessed by cell proliferation and viability with L929 mouse areolar/adipose fibroblasts. Polymer 1 and poly(ethylene glycol) (PEG) were diluted to concentrations from 10(-4) to 10(-6) M in culture media, whereas the degradation products were diluted to concentrations (10(-4) to 10(-6) M) that would theoretically occur upon degradation of polymer 1. The polymer degradation products that were evaluated included mucic acid, hexanoic acid, 1,1,1-tris(4-hydroxyphenyl)ethane (THPE), 2,3,4,5-tetrakis-hexanoyloxy-hexanedioic acid or MA(hex), Core(hex), and PEG5, which is PEG of molecular weight 5000. Cells exposed to polymer 1 proliferated at the same rate as cells grown in polymer-free or PEG5-containing solutions up to 36 h. In both the polymer 1 and PEG5 solutions, cytotoxicity was not observed at any concentration (up to 10(-4) M) as indicated by cell attachment, growth, and morphology. Fibroblasts exposed to the degradation products fared as well as fibroblasts in contact with polymer 1 and PEG5, except for cells exposed to the highest concentration (10(-4) M) of THPE.