Acyclovir-Loaded Chitosan Nanospheres from Nano-Emulsion Templating for the Topical Treatment of Herpesviruses Infections.

Manuela Donalisio,David Lembo,Rita Spagnolo,Andrea Civra,Roberta Cavalli,Ozgen Ozer,Federica Leone

doi:10.3390/pharmaceutics10020046

Manuela Donalisio, David Lembo + Show 5 more

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https://doi.org/10.3390/pharmaceutics10020046

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Abstract

Acyclovir is not a good candidate for passive permeation since its polarity and solubility limit is partitioning into the stratum corneum. This work aims to develop a new topical formulation for the acyclovir delivery. New chitosan nanospheres (NS) were prepared by a modified nano-emulsion template method. Chitosan NS were characterized by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), and an in vitro release study. The in vitro skin permeation experiment was carried out using Franz cells and was equipped with porcine skin. Biological studies were performed on the Vero cell line infected by HSV-1 and HSV-2 strains. The acyclovir loaded chitosan NS appeared with a spherical shape, a size of about 200 nm, and a negative zeta potential of about 40.0 mV. The loading capacity of the drug was about 8.5%. In vitro release demonstrated that the percentage of acyclovir delivered from the nanospheres was approximately 30% after six hours. The in vitro skin permeation studies confirmed an improved amount of permeated acyclovir. The acyclovir-NS complex displayed a higher antiviral activity than that of free acyclovir against both the HSV-1 and the HSV-2 strain. The acyclovir-loaded NS showed no anti-proliferative activity and no signs of cytotoxicity induced by NS was detected. Confocal laser scanning microscopy confirmed that the NS are taken up by the cells.

Highlights

Herpesviruses are responsible for chronic, life-long viral infections that range from asymptomatic infections or mild cutaneous and mucocutaneous lesions up to severe clinical manifestations as encephalitis and aseptic meningitis mainly in immunocompromised individuals and newborns [1]
Chitosan nanospheres were designed as delivery systems for acyclovir topical administration
Chitosan-based nanocarriers have been widely studied for the unique properties of this polymer and, in particular, for its capability to interact with various epithelia and muco-adhesion properties

Summary

Introduction

Herpesviruses are responsible for chronic, life-long viral infections that range from asymptomatic infections or mild cutaneous and mucocutaneous lesions up to severe clinical manifestations as encephalitis and aseptic meningitis mainly in immunocompromised individuals and newborns [1]. After the primary infection of the skin or mucosa, viruses establish latency into root ganglia and may intermittently reactivate causing recurrent episodes with or without clinical signs. HSV-1 primary infections generally occur during childhood as asymptomatic infections or as herpetic gingivostomatitis conditions while recurrent manifestations appear as orolabial lesions, which are called cold sores, fever blisters, or generally herpes labialis. HSV-2, which is mainly sexually transmitted, is responsible for genital herpes, which affected an estimated 417 million people worldwide in 2012 [1,2]. The HSV-2 infection increases the risk of acquiring an HIV infection by approximately three-fold and genital herpes can occur in 60–90% of HIV-infected people [3]. Initial genital herpes episodes caused by HSV-1 are increasing especially among young people [4]

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