title: Encapsulation of Acyclovir in new carboxylated cyclodextrin-based nanosponges improves the agent's antiviral efficacy.
abstract: Cyclodextrin-based nanosponges (NS) are solid nanoparticles, obtained from the cross-linking of cyclodextrins that have been proposed as delivery systems for many types of drugs. Various NS derivatives are currently under investigation in order that their properties might be tuned for different applications. In this work, new carboxylated cyclodextrin-based nanosponges (Carb-NS) carrying carboxylic groups within their structure were purposely designed as novel Acyclovir carriers. TEM measurements revealed their spherical shape and size of about 400 nm. The behaviour of Carb-NS, with respect to the incorporation and delivery of Acyclovir, was compared to that of NS, previously investigated as a drug carrier. DSC, XRPD and FTIR analyses were used to investigate the two NS formulations. The results confirm the incorporation of the drug into the NS structure and NS-Acyclovir interactions. The Acyclovir loading into Carb-NS was higher than that obtained using NS, reaching about 70% (w/w). In vitro release studies showed the release kinetics of Acyclovir from Carb-NS to be prolonged in comparison with those observed with NS, with no initial burst effect. The NS uptake into cells was evaluated using fluorescent Carb-NS and revealed the nanoparticle internalisation. Enhanced antiviral activity against a clinical isolate of HSV-1 was obtained using Acyclovir loaded in Carb-NS.
authors.affiliation: Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino Ospedale S. Luigi Gonzaga,10043 Orbassano, Torino, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Lembo
authors.forename: Shankar
authors.initials: S
authors.lastname: Swaminathan
authors.forename: Manuela
authors.initials: M
authors.lastname: Donalisio
authors.forename: Andrea
authors.initials: A
authors.lastname: Civra
authors.forename: Linda
authors.initials: L
authors.lastname: Pastero
authors.forename: Dino
authors.initials: D
authors.lastname: Aquilano
authors.forename: Pradeep
authors.initials: P
authors.lastname: Vavia
authors.forename: Francesco
authors.initials: F
authors.lastname: Trotta
authors.forename: Roberta
authors.initials: R
authors.lastname: Cavalli
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002264:Carboxylic Acids / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003432:Cross-Linking Reagents / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D014709:Vero Cells; D010948:Viral Plaque Assay; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D002264:Carboxylic Acids; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D000212:Acyclovir