Immobilization of aminothiols on poly(oxyalkylene phosphates). Formation of poly(oxyethylene phosphates)/cysteamine complexes and their radioprotective efficiency.
The necessity to apply near-toxic amounts of radioprotective drugs to achieve adequate protection during radiation treatments represents a major problem in human medicine. One of the promising strategies to suppress the toxicity of these drugs involves their incorporation into biocompatible polymers. In this study cysteamine (Cy) was attached to poly(oxyethylene phosphate), POEP, via an ionic bond. Radioprotection of E. coli B cells by this substance and its acute toxicity on male C57 BL mice were measured. The toxicity of Cy immobilized within the poly(oxyethylene phosphate) was significantly lower in comparison to pure Cy while its radioprotective efficiency remained high at half the maximum tolerable dose. The high radioprotective efficiency of the Cy/POEP complexes was further confirmed on mice at different polymer molecular weight characteristics, drug immobilization degrees, application times, and doses. It was found that POEP with molecular weight 4700 Da and containing 24% repeating units with attached Cy has the highest protection potential combined with a depot effect.
Georgieva
Radostina
R
Department of Radiobiology, National Center of Radiobiology and Radiation Protection, 132 Kl. Ohridski Boulevard, Sofia 1756, Bulgaria.
Tsevi
Raina
R
Kossev
Krassimir
K
Kusheva
Rossitsa
R
Balgjiska
Mariana
M
Petrova
Radostina
R
Tenchova
Violeta
V
Gitsov
Ivan
I
Troev
Kolio
K
D000818:Animals; D003543:Cysteamine / Q000737:chemistry*; D004337:Drug Carriers; D004926:Escherichia coli / Q000187:drug effects / Q000528:radiation effects; D005026:Ethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D051379:Mice; D010755:Organophosphates / Q000138:chemical synthesis / Q000737:chemistry*; D011837:Radiation-Protective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015996:Survival Rate; D023382:Toxicity Tests, Acute; D014916:Whole-Body Irradiation
D004337:Drug Carriers; D005026:Ethylene Glycols; D010755:Organophosphates; D011837:Radiation-Protective Agents; D003543:Cysteamine