Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies

Abstract

Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for effective treatment of herpes virus infections. To increase nanoparticle residence time after local application, semi solid formulations designed from generally regarded as safe (GRAS) excipients were investigated for their rheological and mechanical properties followed with ex vivo mucoadhesive behavior to the porcine vaginal mucosa. Particular effort was made to evaluate the activity of nanoparticle-based hydrogels toward herpes simplex virus (HSV) type 1 and 2 infection in vitro in immortal human keratinocyte cell line and in vivo using murine model of HSV-2 genital infection. The effect of infectivity was determined by real time quantitative polymerase chain reaction, plaque assay, inactivation, attachment, penetration and cell-to-cell assessments. All analyzed nanoparticle-based hydrogels exhibited pseudoplastic and thixotropic properties. Viscosity and mechanical measurements of hydrogels were found to correlate with the mucoadhesive properties. The results confirmed the ability of nanoparticle-based hydrogels to affect viral attachment, impede penetration and cell-to-cell transmission, although profound differences in the activity evoked by tested preparations toward HSV-1 and HSV-2 were noted. In addition, these findings demonstrated the in vivo potential of tannic acid modified silver nanoparticle-based hydrogels for vaginal treatment of HSV-2 genital infection.

Antiviral Activity of Tannic Acid Modified Silver Nanoparticles: Potential to Activate Immune Response in Herpes Genitalis

“…The interaction between tannic-acid modified silver nanoparticles and the virus surface in vitro is much faster than with tannic acid alone [ 19 ]. Furthermore, TA-AgNPs applied both as a colloid or in an appropriate mucoadhesive gel efficiently inhibit HSV-2 infection in the mouse model [ 19 , 20 ]. However, the antiviral properties of TA-AgNPs depend strongly on the size of the nanoparticles, with 20–40 nm silver nanoparticles being the most effective, without undesired toxic and pro-inflammatory properties when applied in vivo [ 19 ].…”

“…AgNPs (100 ppm) sized 33 nm were synthesized by the chemical reduction method in water. This synthesis procedure was described previously [ 19 , 20 ], and it was as follows: a reducing mixture was added to the aqueous solution of silver nitrate, which was heated to boiling point under a reflux. After a few minutes, the solution changed to a brownish color, indicating the formation of AgNPs.…”

“…We have previously described the anti-HSV-2 activity of tannic acid modified AgNPs (TA-AgNPs) by using both in vitro and in vivo models [ 19 , 20 ]. The mechanisms of the antiviral action of TA-AgNPs includ blocking the virus attachment and entry, as well as the induction of anti-viral cytokine and chemokine production.…”

Antiviral Potential of Nanoparticles—Can Nanoparticles Fight Against Coronaviruses?

“…Zanamivir-loaded AgNPs synergistically inhibited H1N1 influenza virus multiplication [80]. Tannic acid-modified AgNP-based muco-adhesive hydrogel effectively reduced HSV-2 infectivity at the vaginal mucosal surface [81]. AgNPs exhibited antiviral activity against human oncogenic γ-herpesviruses, Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus by reactivating viral lytic replication through the generation of reactive oxygen species (ROS) and autophagy [82].…”

An overview of functional nanoparticles as novel emerging antiviral therapeutic agents

“…One of the effective solutions is hydrogel, a semisolid preparation that can broaden the application field of silver nanoparticle-based reagents. For instance, Szyma'nska et al have developed a multifunctional tannic acid-modified silver nanoparticle-based mucoadhesive hydrogel for improving the local treatment of herpes simplex virus (HSV) infections [63]. The silver nanoparticles modified with tannic acid (TA-AgNPs) were shown to effectively reduce the HSV-2 infectivity at the vaginal mucosal surface, suggesting the potential use of functional nanoparticles as microbicides in HSV prevention.…”