Slow releasing of ara-C from poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate-co-N-vinyl-2-pyrrolidone) hydrogels implanted subcutaneously in the back of rats.
The release of cytarabine (ara-C) from poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate-co-N-vinyl-2pyrrolidone) hydrogels cross-linked with different amounts of ethyleneglycol dimethacrylate (EGDMA) 'in vivo' has been studied. Two ara-C loaded hydrogel discs, each with 25 mg of the drug, were subcutaneously implanted in the back of male Wistar rats. Total ara-C dose was 230 mg kg(-1). Ara-C and ara-U plasmatic concentration were determined by HPLC. Periods of constant drug concentration are observed from all gels. Ara-C concentrations in the steady-state are between 19.0 +/- 2.0 and 2.2 +/- 0.8 micromol l(-1). The release time of ara-C was between 3 days from pH EMA 0.5% and 16 days from H80/VP20/E15 gels. These results are very different of that obtained when ara-C is administered by intraperitoneal injection, in this case peaks of maximum concentration (between 24 +/- 1 and 3.9 +/- 0.4 microg ml(-1)) 30 min after the injection are originated, and no drug is detected 4 h after the injection.
Blanco
M D
MD
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Trigo
R M
RM
Teijón
C
C
Gómez
C
C
Teijón
J M
JM
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000097:blood* / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D003561:Cytarabine / Q000008:administration & dosage* / Q000097:blood* / Q000737:chemistry; D003692:Delayed-Action Preparations; D004343:Drug Implants; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007274:Injections, Intraperitoneal; D008297:Male; D008689:Methacrylates / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry*; D011102:Polyhydroxyethyl Methacrylate / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry*; D011205:Povidone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D000964:Antimetabolites, Antineoplastic; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004343:Drug Implants; D008689:Methacrylates; C114441:poly(2-hydroxyethyl methacrylate-co-N-vinyl-2-pyrrolidone); D003561:Cytarabine; D011102:Polyhydroxyethyl Methacrylate; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; C004919:ethylene dimethacrylate; D011205:Povidone