Preclinical development of biodegradable polymer foils for intracerebral delivery of cytotoxic nucleosides.
Intracerebral implantation of biodegradable polymers loaded with cytotoxic or radiosensitising nucleoside analogues is a promising treatment strategy for malignant gliomas, which are currently intractable. The aim of the study was to develop biodegradable polymers containing nucleosides which could be implanted intracerebrally. Methods of synthesis were developed for the copolymers composed of D,L-lactide, glycolide and caprolactone in different proportions, as well as a novel method of introducing nucleosides to these copolymers at the polymerisation step. Upon degradation in an aqueous medium some of these copolymers emit nucleosides in micromolar concentration over several months. Their in situ degradation and biocompatibility with brain tissues was assessed by means of scanning and transmission electron microscopy. At the ultrastructural level tissue responses to the copolymer implantation closely resembled the responses to mechanical trauma.
Grieb
Paweł
P
Laboratory of Experimental Pharmacology, Medical Research Centre, Polish Academy of Science, Warszawa, Poland. pgrieb@cmdik.pan.pl
Ryba
Mirosław
M
Janisz
Monika
M
Walski
Michał
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000648:ultrastructure; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007276:Injections, Intraventricular; D008297:Male; D009705:Nucleosides / Q000008:administration & dosage* / Q000633:toxicity*; D011108:Polymers / Q000008:administration & dosage*; D051381:Rats; D013678:Technology, Pharmaceutical / Q000379:methods*
D009705:Nucleosides; D011108:Polymers