Enhanced Anti-Herpetic Activity of Valacyclovir Loaded in Sulfobutyl-ether-β-cyclodextrin-decorated Chitosan Nanodroplets

Valacyclovir (VACV) was developed as a prodrug of the most common anti-herpetic drug Acyclovir (ACV), aiming to enhance its bioavailability. Nevertheless, prolonged VACV oral treatment may lead to the development of important side effects. Nanotechnology-based formulations for vaginal administration...

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Published inMicroorganisms (Basel) Vol. 11; no. 10; p. 2460
Main Authors Argenziano, Monica, Arduino, Irene, Rittà, Massimo, Molinar, Chiara, Feyles, Elisa, Lembo, David, Cavalli, Roberta, Donalisio, Manuela
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 30.09.2023
MDPI
Subjects
Acids
Acyclovir
Antiviral activity
Bioavailability
Care and treatment
Chitin
Chitosan
chitosan nanodroplets
Cloning
Complications and side effects
Controlled release
Cyclodextrins
Dosage and administration
Herpes
Herpes simplex
Herpes viruses
Herpesvirus diseases
HIV
HSV-2 infection
Human immunodeficiency virus
Infections
Laboratories
Molecular weight
Nanotechnology
Physiological aspects
Side effects
sulfobutyl ether-β-cyclodextrin
Sustained release
Toxicity
Vagina
Valacyclovir
β-Cyclodextrin
Italy
United States > US
Germany
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Abstract Valacyclovir (VACV) was developed as a prodrug of the most common anti-herpetic drug Acyclovir (ACV), aiming to enhance its bioavailability. Nevertheless, prolonged VACV oral treatment may lead to the development of important side effects. Nanotechnology-based formulations for vaginal administration represent a promising approach to increase the concentration of the drug at the site of infection, limiting systemic drug exposure and reducing systemic toxicity. In this study, VACV-loaded nanodroplet (ND) formulations, optimized for vaginal delivery, were designed. Cell-based assays were then carried out to evaluate the antiviral activity of VACV loaded in the ND system. The chitosan-shelled ND exhibited an average diameter of about 400 nm and a VACV encapsulation efficiency of approximately 91% and was characterized by a prolonged and sustained release of VACV. Moreover, a modification of chitosan shell with an anionic cyclodextrin, sulfobutyl ether β-cyclodextrin (SBEβCD), as a physical cross-linker, increased the stability and mucoadhesion capability of the nanosystem. Biological experiments showed that SBEβCD-chitosan NDs enhanced VACV antiviral activity against the herpes simplex viruses type 1 and 2, most likely due to the long-term controlled release of VACV loaded in the ND and an improved delivery of the drug in sub-cellular compartments.
AbstractList Valacyclovir (VACV) was developed as a prodrug of the most common anti-herpetic drug Acyclovir (ACV), aiming to enhance its bioavailability. Nevertheless, prolonged VACV oral treatment may lead to the development of important side effects. Nanotechnology-based formulations for vaginal administration represent a promising approach to increase the concentration of the drug at the site of infection, limiting systemic drug exposure and reducing systemic toxicity. In this study, VACV-loaded nanodroplet (ND) formulations, optimized for vaginal delivery, were designed. Cell-based assays were then carried out to evaluate the antiviral activity of VACV loaded in the ND system. The chitosan-shelled ND exhibited an average diameter of about 400 nm and a VACV encapsulation efficiency of approximately 91% and was characterized by a prolonged and sustained release of VACV. Moreover, a modification of chitosan shell with an anionic cyclodextrin, sulfobutyl ether β-cyclodextrin (SBEβCD), as a physical cross-linker, increased the stability and mucoadhesion capability of the nanosystem. Biological experiments showed that SBEβCD-chitosan NDs enhanced VACV antiviral activity against the herpes simplex viruses type 1 and 2, most likely due to the long-term controlled release of VACV loaded in the ND and an improved delivery of the drug in sub-cellular compartments.
Audience Academic
Author Donalisio, Manuela
Arduino, Irene
Lembo, David
Cavalli, Roberta
Molinar, Chiara
Feyles, Elisa
Argenziano, Monica
Rittà, Massimo
AuthorAffiliation 2 Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy; massimo.ritta@unito.it (M.R.); elisa.feyles@unito.it (E.F.); manuela.donalisio@unito.it (M.D.)
1 Department of Drug Science and Technology, University of Turin, Via P. Giuria 9, 10100 Torino, Italy; monica.argenziano@unito.it (M.A.); chiara.molinar@unito.it (C.M.); roberta.cavalli@unito.it (R.C.)
AuthorAffiliation_xml – name: 2 Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy; massimo.ritta@unito.it (M.R.); elisa.feyles@unito.it (E.F.); manuela.donalisio@unito.it (M.D.)
– name: 1 Department of Drug Science and Technology, University of Turin, Via P. Giuria 9, 10100 Torino, Italy; monica.argenziano@unito.it (M.A.); chiara.molinar@unito.it (C.M.); roberta.cavalli@unito.it (R.C.)
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Snippet Valacyclovir (VACV) was developed as a prodrug of the most common anti-herpetic drug Acyclovir (ACV), aiming to enhance its bioavailability. Nevertheless,...
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StartPage 2460
SubjectTerms Acids
Acyclovir
Antiviral activity
Bioavailability
Care and treatment
Chitin
Chitosan
chitosan nanodroplets
Cloning
Complications and side effects
Controlled release
Cyclodextrins
Dosage and administration
Herpes
Herpes simplex
Herpes viruses
Herpesvirus diseases
HIV
HSV-2 infection
Human immunodeficiency virus
Infections
Laboratories
Molecular weight
Nanotechnology
Physiological aspects
Side effects
sulfobutyl ether-β-cyclodextrin
Sustained release
Toxicity
Vagina
Valacyclovir
β-Cyclodextrin
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Title Enhanced Anti-Herpetic Activity of Valacyclovir Loaded in Sulfobutyl-ether-β-cyclodextrin-decorated Chitosan Nanodroplets
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https://pubmed.ncbi.nlm.nih.gov/PMC10609596
https://doaj.org/article/a1d8ae64ade541d8b13dea88f9dd5a22
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