Preparation and in vitro evaluation of the antiviral activity of the Acyclovir complex of a beta-cyclodextrin/poly(amidoamine) copolymer.
A poly(amidoamine) (PAA) copolymer with beta-cyclodextrin was obtained by polyaddition reaction of 6-deoxy-6-amino-beta-cyclodextrin (beta-CD-NH(2)) and 2-methylpiperazine to 2,2-bis(acrylamido)acetic acid in aqueous medium. This beta-CD/PAA copolymer bears beta-CD units along the macromolecular chain, is water-soluble and non-cytotoxic. The complexing capacity of beta-CD/PAA was determined using an antiviral drug, Acyclovir, as a model of poorly water-soluble drug. Complex formation was confirmed by means of DSC and FTIR analyses. beta-CD/PAA can solubilize up to 11% w/w of Acyclovir notably increasing the aqueous solubility of the drug. The in vitro release studies showed the dependence of Acyclovir release rate on the solution pH. The antiviral activity of Acyclovir beta-CD/PAA complex was evaluated against herpes simplex virus type I in cell cultures. The Acyclovir beta-CD/PAA complex exhibited a higher antiviral activity than the free drug.
Bencini
Marco
M
Dipartimento di Chimica Organica e Industriale, and Centro Interdisciplinare Materiali e Interfacce Nanostrutturati (CIMAINA) Università di Milano, via Venezian 21, 20133 Milano, Italy.
Ranucci
Elisabetta
E
Ferruti
Paolo
P
Trotta
Francesco
F
Donalisio
Manuela
M
Cornaglia
Maura
M
Lembo
David
D
Cavalli
Roberta
R
D000212:Acyclovir / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D018259:Herpesvirus 1, Human / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry*; D012995:Solubility; D014709:Vero Cells; D047392:beta-Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry*
D000998:Antiviral Agents; D004337:Drug Carriers; D011073:Polyamines; D047392:beta-Cyclodextrins; C527738:beta-cyclodextrin-poly(amidoamine) copolymer; D000212:Acyclovir