Syntheses, chemical and enzymatic stability of new poly(ethylene glycol)-acyclovir prodrugs.
Two known antiherpetic agents, acyclovir and valaciclovir, were coupled with activated poly(ethylene glycol). In vitro drug release studies demonstrated the conjugates to be stable in buffer solutions at pH 7.4 and 5.5, while only PEG-valacyclovir2 was stable in a buffer solution at pH 1.2. The ability of the macromolecular conjugate to release the free drug was also evaluated in plasma, in which the most stable prodrug also proved to be PEG-valacyclovir2. The derivatives are degraded in the presence of proteolytic enzyme. The rate of hydrolysis was monitored by HPLC-analysis.
Zacchigna
M
M
Department of Pharmaceutical Sciences, University of Trieste, Italy. zacchign@univ.trieste.it
Di Luca
G
G
Maurich
V
V
Boccù
E
E
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000097:blood / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011485:Protein Binding / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics
D000998:Antiviral Agents; D004337:Drug Carriers; D011355:Prodrugs; D011092:Polyethylene Glycols; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir