New bioerodable thermoresponsive polymers for possible radiotherapeutic applications

A new thermoresponsive system designed for local radiotherapy has been developed. In this system a radionuclide complex is entrapped in a thermoresponsive polymer locally precipitated at body temperature after injection of a polymer–complex solution into the tissue where a therapeutic effect is requ...

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Bibliographic Details
Published in:Journal of controlled release 2007-05, Vol.119 (1), p.25-33
Main Authors: Hruby, Martin, Kucka, Jan, Lebeda, Ondrej, Mackova, Hana, Babic, Michal, Konak, Cestmir, Studenovsky, Martin, Sikora, Antonin, Kozempel, Jan, Ulbrich, Karel
Format: Article
Language:English
Subjects:
bioerodable
Biological and medical sciences
Biotransformation
Body Temperature
drug delivery
Drug Delivery Systems - methods
Drug Delivery Systems - trends
General pharmacology
Medical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
polymer
Polymers - administration & dosage
Polymers - chemistry
Polymers - metabolism
radiotherapy
Radiotherapy - methods
Radiotherapy - trends
Temperature
thermoresponsive
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Summary:A new thermoresponsive system designed for local radiotherapy has been developed. In this system a radionuclide complex is entrapped in a thermoresponsive polymer locally precipitated at body temperature after injection of a polymer–complex solution into the tissue where a therapeutic effect is required. The lifetime of the system is controlled by the rate of polymer hydrolysis, its dissolution and elimination from the body. The thermoresponsive polymer with the cloud temperature (CT) below body temperature is based on copolymers of N-isopropylmethacrylamide with a methacrylamide-type comonomer containing hydrophobic n-alkyls of three different sizes (C 3, C 6 and C 12) bonded by a hydrolytically labile hydrazone bond. Hydrolysis of hydrazone bond results in a copolymer soluble at body temperature. The copolymer containing 27.5 mole% of the comonomer with the C 6 moiety, which was chosen for further study, has the CT 22 °C and its phase separation is complete at 34 °C. Polymer dissolution is complete within 48 h at both pH 5.0 or 7.4. The model therapeutic radionuclide, 64Cu, in the form of its hydrophobic chelate bis(quinolin-8-olato- N, O) [ 64Cu]copper, is efficiently kept hydrophobically entrapped in the phase-separated polymer until the dissolution by hydrolytic degradation is completed.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2007.02.009