New derivatives of polyglutamic acid as drug carrier systems.
PEG-grafted dextran and PHEG derivatives were synthetized to be used as drug carriers. The PEG-containing copolymers showed potential tensioactive properties. Dynamic light-scattering measurements and surface tension measurements indicated that phase separation of dextran/PHEG and PEG occurs on a molecular level in the conjugates and results in the formation of aggregates with a PEG core in which free PEG can be trapped. Blood clearance and body distribution studies were performed on female BALB/c mice. PEG-modified polymers with a high hydrodynamic volume stay longer in the blood stream compared with the non-modified polymers. These high molecular weight conjugates stay in the blood for several hours. Conjugates with a molecular weight below the renal threshold barrier are cleared much faster from the blood and excreted from the body. Concerning the body distribution, the PEG conjugates are not excreted very fast and are not taken up by any organ in particular. It is notable that PEG substitution prevents dextran from liver uptake. Furthermore, a method was developed to link an oligopeptide spacer-drug model and PEG to the same polymer. It was shown that PEG substitution has only little influence on the enzymatic release of the model drug. The above-mentioned results showed that the PEG-grafted polymers were promising candidates for drug carriers.
Hoste
K
K
Polymer Materials Research Group, University of Ghent, Krijgslaan 281, 9000, Ghent, Belgium.
Schacht
E
E
Seymour
L
L
D000818:Animals; D003911:Dextrans / Q000097:blood*; D004337:Drug Carriers / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000097:blood* / Q000138:chemical synthesis; D010952:Plasma Substitutes / Q000493:pharmacokinetics; D011099:Polyglutamic Acid / Q000097:blood*; D013500:Surface Tension; D013997:Time Factors; D014018:Tissue Distribution
D003911:Dextrans; D004337:Drug Carriers; D009842:Oligopeptides; D010455:Peptides; D010952:Plasma Substitutes; D011099:Polyglutamic Acid; C027887:poly-N(5)-(2-hydroxyethyl)glutamine