Comparison of Bioabsorbable Poly(ester-amide) Monomers and Polymers In Vivo Using Radiolabeled Homologs
Poly(ester-amides) (PEA) are a class of bioabsorbable polymers with potential biomedical applications. To evaluate the in vivo degradation and elimination routes of these polymers, rats were implanted with a carbon-14 labeled monomer precursor, C6 −, C10 −, C12 −, or Coxy-amidediol, or PEA-2,12 polymer and excreta and tissues were examined radiometrically; a comparison to the previously studied PEA-2,6 polymer was also made. Urinary excretion was a major route of amidediol elimination; the greater the water solubility of the amidediol, the faster and more extensively it was excreted unchanged in the urine. Conversely, the more hydrophobic the amidediol, the greater was its fecal excretion and the degree of biotransformation that occurred. Radiolabeled residues in tissues were low for each amidediol, indicating minimal deposition. Similar trends in elimination routes and rates were also observed upon comparing PEA-2,12 polymer with the previously studied PEA-2,6 polymer. The urine was the major route of excretion for both polymers. The more hydrophobic PEA-2,12 polymer was, overall, eliminated slower and excreted to a lesser extent in the urine, with a larger number of putative metabolites seen, than the more hydrophilic PEA-2,6 polymer. A sex-related difference was observed in PEA-2,12 polymer metabolism; female rats excreted more radiolabel as exhaled 14CO2 while males eliminated more of the dose in the feces. While female rats had higher radiolabel tissue concentrations than males, these concentrations were still relatively low at 3, 6, 9 and 12 months after the dose of PEA-2,12, suggesting little potential for significant tissue accumulation of polymer breakdown products.
KeywordsFecal Excretion Elimination Route Subcutaneous Dose Polymer Hydrolysis Polymer Dose
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