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.
Highlights
Herpes simplex virus (HSV), classified as type 1 and 2, is highly prevalent contagious pathogen affecting skin and mucosal tissues of up to 67% of adolescents and adults worldwide [1,2]
It was previously demonstrated that silver nanoparticles stabilized with tannic acid displayed antiviral activity and potential as microbicide for prevention and treatment of HSV-2 infection [15,19]
The results presented in this study indicate that hydrogels with TA-AgNPs possess distinctive ability to prevent both HSV-1 and HSV-2 infection by direct inhibition of viral attachment, penetration and post-infection spread
Summary
Herpes simplex virus (HSV), classified as type 1 and 2, is highly prevalent contagious pathogen affecting skin and mucosal tissues of up to 67% of adolescents and adults worldwide [1,2]. HSV-2 infections, which are more common in women than in men [5,6], were found to be closely associated with elevated risk of acquiring and transmitting HIV infection [7]. Both types of HSV persist in a latent state within the cell nucleus with the risk of periodical reactivation especially in patients with weakened immune system [8]. The potential hazard of HSV transmission is increased considerably among people with asymptomatic shedding
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