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

Monica Argenziano; Irene Arduino; Massimo Rittà; Chiara Molinar; Elisa Feyles; David Lembo; Roberta Cavalli; Manuela Donalisio

doi:10.3390/microorganisms11102460

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

Microorganisms. 2023 Sep 30;11(10):2460. doi: 10.3390/microorganisms11102460.

Authors

Monica Argenziano¹, Irene Arduino², Massimo Rittà², Chiara Molinar¹, Elisa Feyles², David Lembo², Roberta Cavalli¹, Manuela Donalisio²

Affiliations

¹ Department of Drug Science and Technology, University of Turin, Via P. Giuria 9, 10100 Torino, Italy.
² Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy.

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.

Keywords: HSV-2 infection; chitosan nanodroplets; sulfobutyl ether-β-cyclodextrin; valacyclovir.

Grants and funding

This research was funded by University of Turin to R.C., M.A. and M.D., and by EU funding to D.L. within the MUR PNRR Extended Partnership Initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT).