Copolymers of N-(2-hydroxypropyl)methacrylamide containing oligopeptidic sequences either in side chains or as part of crosslinks were prepared. These polymers were applied intravenously to rats, and spectrophotometric analysis (oligopeptidic side chains) or gel permeation chromatography of urine (oligopeptidic crosslinks) have shown that both types of polymers are cleavable in vivo.
0025-1 16X/8 1/0182/2941/%03 .00 *) Abbreviations: All amino acids are of L-configuration. Abbreviations used are those recommended by IUPAC-IUB, cf. J. Biol. Chem. 247, 977 (1972).
Two poly(amino acid) systems were studied: (a) poly[N5‐(2‐hydroxyethyl)‐L‐glutamine] (PHEG) derivatives prepared by NCA polymerization; (b) poly‐α,β‐[N‐(2‐hydroxyethyl)‐DL‐aspartamide] (PHEA) derivatives prepared by thermal polycondensation of aspartic acid to racemic polysuccinimide followed by chemical modification reactions. The degradation of polymers by isolated enzymes and homogenate of kidney tissue was studied in vitro and the effect of polymer structure on the rate of degradation and the size of degradation products was evaluated. A PHEA derivative (modified by tyramine residues in 9.6 % of side chains) was accumulated in the lysosomes of kidney cells of rats and the molecular‐weight distribution of the polymer retained inside the lysosomes of living cells and that of the polymer excreted into urine was analysed by a high‐sensitivity size‐exclusion chromatography using the fluorescence and radioactive labelling. While PHEG derivatives were degraded by isolated mammalian enzymes and a tissue homogenate, no significant degradation of PHEA and derivatives was observed, either in vitro, with isolated enzymes and homogenate or in vivo, under a long‐term exposure to the lysosomal enzymes in living cells.
Poly(2-hydroxyethyl methacrylate) gels obtained by the cross-linking polymerization using four different free-radical initiators were washed with water. Chromatographically, the eluate appeared to be a mixture of low-molecular-weight compounds and of a small amount of the high-molecular-weight component. The UV and IR absorption spectra of compounds present in the eluate were compared with those of model compounds that were assumed to exist in the gel as impurities after the polymerization (monomers and oligomers of hydroxyethyl methacrylate, decomposition products of initiators). Time dependences of the removal of impurities from the gels by washing were measured. Most of the impurities were washed out within a few hours. In addition to the assumed impurities, the eluate was found to contain an unidentified compound that was still washed out after several months. Intracutaneous applications of this compound did not produce local irritation of the tested tissue.
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