Poly(acrylamide-co-monoethyl itaconate) hydrogels as devices for cytarabine release in rats

J Pharm Pharmacol. 1998 Jul;50(7):703-12. doi: 10.1111/j.2042-7158.1998.tb07130.x.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / chemistry*
  • Acrylamides / metabolism
  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / pharmacokinetics*
  • Cytarabine / administration & dosage
  • Cytarabine / pharmacokinetics*
  • Diffusion
  • Drug Carriers
  • Drug Implants
  • Hydrogels / chemistry*
  • Male
  • Rats
  • Rats, Wistar
  • Succinates / chemistry*
  • Succinates / metabolism
  • Therapeutic Equivalency

Substances

  • Acrylamides
  • Antimetabolites, Antineoplastic
  • Drug Carriers
  • Drug Implants
  • Hydrogels
  • Succinates
  • poly(acrylamide-co-monoethyl itaconate)
  • Cytarabine