title: Synthesis and physico-chemical characterization of a β-cyclodextrin conjugate for sustained release of Acyclovir.
abstract: We report the synthesis of an oligomeric prodrug of the antiviral agent Acyclovir (Acy) conjugated to β-cyclodextrin (β-CyD). The drug was selectively linked through a succinic spacer to one of the primary hydroxyl groups of β-CyD by ester linkage in a 1:1 molar ratio. The conjugate was purified by semipreparative reverse-phase chromatography and characterized by FAB mass spectrometry and NMR experiments. The release of Acy from the conjugate was evaluated both in acidic and in neutral conditions and in the presence of porcine liver esterase. In all cases we observed the release of both free Acy and Acy succinate (AcySucc) at differing rates as a function of the hydrolysis conditions. In the presence of esterase the release of free Acy was favoured over AcySucc, showing a release rate of 100% of Acy within 7 days.
authors.affiliation: CNR-Istituto di Chimica Biomolecolare, Via Paolo Gaifami 18, I-95126 Catania, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Pedotti
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy. Electronic address: vpistara@unict.it.
authors.forename: Venerando
authors.initials: V
authors.lastname: Pistarà
authors.affiliation: Dipartimento di Patologia Umana, Università di Messina, Policlinico Universitario, Pad. H, Via Consolare Valeria 1, I-98125 Messina, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Cannavà
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Carbone
authors.affiliation: Dipartimento di Scienze della Salute, Università "Magna Græcia" di Catanzaro, Viale Europa, I-88100 Catanzaro, Italy.
authors.forename: Felisa
authors.initials: F
authors.lastname: Cilurzo
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Corsaro
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Puglisi
authors.affiliation: Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute (SCIFAR), Università di Messina, Viale Annunziata, I-98168 Messina, Italy. Electronic address: caventura@unime.it.
authors.forename: Cinzia Anna
authors.initials: CA
authors.lastname: Ventura
mesh_terms: D000212:Acyclovir / Q000494:pharmacology*; D055598:Chemical Phenomena; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D047392:beta-Cyclodextrins; C031215:betadex; D000212:Acyclovir
keywords: Acyclovir; Drug release; NMR experiments; β-Cyclodextrin conjugate