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

Microbiology

Journal of Antivirals & Antiretrovirals

Author(s): Giammona G, Cavallaro G, Fontana G, Pitarresi G, Carlisi B

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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.
This article was published in J Control Release and referenced in Journal of Antivirals & Antiretrovirals

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