Abstract

Infections due to HSV-1 affect many people all over the world. To counteract this pathology, usually characterized by perioral sores or by less frequent serious symptoms including keratitis, synthetic antiviral drugs are employed, such as acyclovir, often resulting in resistant viral strains under long-term use. Many plant-derived compounds, such as mangiferin and quercetin, have demonstrated antiviral potentials. In this study, smart semisolid forms based on phosphatidylcholine and Pluronic were investigated as delivery systems to administer mangiferin on skin and mucosae affected by HSV-1 infection. Particularly, lecithin organogels, Pluronic gel, and Pluronic lecithin organogels were formulated and characterized. After the selection of gel compositions, physical aspects, such as rheological behavior, spreadability, leakage, and adhesion were evaluated, suggesting a scarce suitability of the lecithin organogel for topical administration. Mangiferin was efficiently included in all type of gels. An in vitro study based on the Franz cell enabled us to find evidence of the gel capability to control drug diffusion, especially in the case of Pluronic organogel, while an in vivo study conducted on human volunteers demonstrated the safeness of all of the gels after cutaneous administration. Furthermore, a plaque reduction assay demonstrated the virucidal effect of mangiferin loaded in a Pluronic gel and a Pluronic lecithin organogel against the HSV-1 KOS strain.

Highlights

  • Herpes simplex virus type 1 (HSV-1) is a common human pathogen affecting billions of people worldwide

  • The formulative study evidenced the suitability of Pluronic gels (PGs) and Pluronic lecithin organogel (PLO)-3 over

  • The formulative study evidenced the suitability of PG and PLO-3 over lecithin organogels (LO)

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Summary

Introduction

Herpes simplex virus type 1 (HSV-1) is a common human pathogen affecting billions of people worldwide. For instance in immunocompromised patients, HSV-1 infection can cause severe complications, including encephalitis or keratitis [4]. To treat HSV-1 infections, many antiviral drugs are in clinical use, among which acyclovir is the first-line drug [5]. The long-term use of acyclovir induces drug-resistant viral strains; new antiviral alternative drugs against drug-resistant HSV-1 are strongly required [6,7]. In this respect many plant extracts widely used in medicine possess interesting therapeutic potential, such as antimicrobial and antiviral activities. Balm mint extracts, Brazilian propolis extracts, rosemary, lemon balm oil, quercetin, and mangiferin (MG) demonstrated and inhibitory activity against HSV-1 [8,9,10,11,12]

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