Enhanced antiviral activity of Acyclovir loaded into beta-cyclodextrin-poly(4-acryloylmorpholine) conjugate nanoparticles.
Novel polymeric nanoparticles based on a beta-cyclodextrin-poly(4-acryloylmorpholine) mono-conjugate (beta-CD-PACM), a tadpole-shaped polymer in which the beta-CD ring is the hydrophilic head and the PACM chain the amphiphilic tail, were prepared by the solvent injection technique. Acyclovir-loaded nanoparticles were prepared from inclusion complexes of Acyclovir with beta-CD-PACM. Both unloaded and drug-loaded nanoparticles were characterized in terms of particle size distribution, morphology, zeta potential, drug loading and in vitro drug release rate. The antiviral activity of Acyclovir loaded into beta-CD-PACM nanoparticles against two clinical isolates of HSV-1 was evaluated and found to be remarkably superior compared with that of both the free drug and a soluble beta-CD-PACM complex reported in a previous paper. Fluorescent nanoparticles loaded with coumarin 6 were also prepared in order to investigate the nanoparticle cell uptake by confocal laser microscopy. It was found that the nanoparticles are internalized in cells and locate in the perinuclear compartment.
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via P.Giuria 9, 10125 Torino, Italy. roberta.cavalli@unito.it
Roberta
R
Cavalli
Manuela
M
Donalisio
Andrea
A
Civra
Paolo
P
Ferruti
Elisabetta
E
Ranucci
Francesco
F
Trotta
David
D
Lembo
D000178:Acrylamides / Q000737:chemistry; D000212:Acyclovir / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003374:Coumarins; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000254:growth & development; D009025:Morpholines / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D013844:Thiazoles; D014709:Vero Cells; D047392:beta-Cyclodextrins / Q000737:chemistry
C527295:4-acryloylmorpholine; D000178:Acrylamides; D000998:Antiviral Agents; D003374:Coumarins; D004337:Drug Carriers; D009025:Morpholines; D011108:Polymers; D013844:Thiazoles; D047392:beta-Cyclodextrins; C517282:coumarin 6; C031215:betadex; D000212:Acyclovir