Coupling of the antiviral agent zidovudine to polyaspartamide and in vitro drug release studies

J Control Release. 1998 Aug 14;54(3):321-31. doi: 10.1016/s0168-3659(98)00020-0.

Abstract

A macromolecular prodrug of the known antiretroviral agent zidovudine and alpha, beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) was synthesized. A succinic spacer was present between the polymer and the drug, and 1,1'-carbonyldiimidazole was used as the coupling agent. In vitro drug release studies at pH 1.1, 5.5 and 7.4 indicated that limited amounts of intact drug were released from the conjugate. At pH 1.1 and 7.4 succinylzidovudine was released, and this was hydrolysed to give free zidovudine. In the presence of alpha-chymotrypsin, zidovudine was released preferentially in comparison with the succinyl derivative. The amounts of released zidovudine and succinylzidovudine were greater in plasma than in aqueous buffer solutions. These results show that after i.v. administration this drug-polymer conjugate can release zidovudine into the blood circulation for prolonged periods.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / chemistry
  • Chymotrypsin / chemistry
  • Drug Carriers
  • Humans
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • In Vitro Techniques
  • Peptides / chemistry*
  • Prodrugs
  • Zidovudine / administration & dosage*
  • Zidovudine / analogs & derivatives*
  • Zidovudine / chemistry

Substances

  • 5'-O-succinylzidovudine
  • Anti-HIV Agents
  • Drug Carriers
  • Peptides
  • Prodrugs
  • alpha,beta-poly((2-hydroxyethyl)-aspartamide)
  • Zidovudine
  • Chymotrypsin