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

• Published in: Microorganisms (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
• Language: English
• 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
• ISSN: 2076-2607; 2076-2607
• DOI: 10.3390/microorganisms11102460

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.