Poly(acrylamide-co-monoethyl itaconate) hydrogels as devices for cytarabine release in rats.
This study has tested the application of three different copolymeric poly(acrylamide-co-monoethyl itaconate; A/MEI) hydrogels, 90A/10MEI, 75A/25MEI and 60A/40MEI, on the release of cytarabine (ara-C). The drug was incorporated in gels by placing it in the polymerization feed mixture and discs loaded with 5-50 mg ara-C were obtained. The amount of swelling at equilibrium in saline solution (NaCl, 0.9% w/w) was between 78 and 82% w/w, depending on the composition of the copolymer. The diffusion studies followed Fick's second law. The diffusion coefficients for swelling of the gels were between 9.30 x 10(-11) m2 s(-1) and 37.42 x 10(-11) m2 s(-1); those for release of ara-C were between 3.42 x 10(-11) m2 s(-1) and 10.25 x 10(-11) m2 s(-1). The activation energies for swelling were in the range 16.60 +/- 2.59-21.85 +/- 1.78 kJ mol(-1); those for ara-C release were 28.13 +/- 3.1-29.7 +/- 4.6 kJ mo(-1). To determine the applicability of these copolymers, 75A/25MEI gel was subcutaneously implanted in rats and the plasma concentration of the drug was determined by high-performance liquid chromatography. The concentration of ara-C in plasma (range 17.67 +/- 5.68-10.76 +/- 2.15 microg mL(-1)) was maintained during the first stages (2-8 h) and no drug was detected after 32 h. This route of administration was compared with intraperitoneal injection of the drug. In conclusion, ara-C can be incorporated in hydrogels and released in a pharmacologically active form. The concentration of ara-C in plasma is maintained for long enough to improve therapeutic results.
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
C
C
Gomez
M D
MD
Blanco
M V
MV
Bernardo
R L
RL
Sastre
J M
JM
Teijón
D000178:Acrylamides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003561:Cytarabine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004058:Diffusion; D004337:Drug Carriers; D004343:Drug Implants; D020100:Hydrogels / Q000737:chemistry*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013386:Succinates / Q000737:chemistry* / Q000378:metabolism; D013810:Therapeutic Equivalency
D000178:Acrylamides; D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D004343:Drug Implants; D020100:Hydrogels; D013386:Succinates; C115639:poly(acrylamide-co-monoethyl itaconate); D003561:Cytarabine