Erbulozole (P.I.N.N.) (R 55 104) encapsulated into cyclodextrins: has it a combined antitumoral and radioprotective potential?
The clinically applicable formulation of the microtubule inhibitor erbulozole (R 55 104), dissolved into an aqueous hydroxypropyl-beta-cyclodextrin solution (designated as R 55 104-CYCLO), exerts a similar effect on growth delay of subcutaneous MO4 fibrosarcomas in mice, with or without 10 Gy gamma-irradiation given locally to the tumors 2 h later, compared to R 55 104 in water. The drug concentration can be reduced from 80 mg/kg to 5 mg/kg without affecting the activity of this particular drug-radiation combination. Furthermore, 80 mg/kg R 55 104-CYCLO show a radioprotective effect when given 2 h before total body irradiation of non-tumor bearing mice. A radiation dose of 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 Gy respectively was given resulting in a LD50(30) of 5.97 Gy for the irradiated mice and 7.65 Gy for the drug-radiation treated animals (Dose Effect Factor = 0.78). Therapeutic implications of both observations are discussed.
Distelmans
W
W
Janssen Research Foundation, Beerse, Belgium.
Van Ginckel
R
R
Vanherck
W
W
Willebrords
R
R
Wouters
L
L
De Brabander
M
M
Mesens
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002214:Capsules; D002455:Cell Division / Q000187:drug effects; D004148:Dioxolanes / Q000627:therapeutic use*; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D005720:Gamma Rays; D051379:Mice; D008815:Mice, Inbred Strains; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy
D000970:Antineoplastic Agents; D002214:Capsules; D004148:Dioxolanes; D011837:Radiation-Protective Agents; C062050:erbulozole