Topical application of polyethylenimine as a candidate for novel prophylactic therapeutics against genital herpes caused by herpes simplex virus

Abstract

Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) cause genital herpes, which can enhance the acquisition of human immunodeficiency virus. The development of anti-HSV agents with novel mechanisms of action is urgently required in the topical therapy of genital herpes. In this study, the in vitro and in vivo anti-HSV effects of Epomin SP-012(®), a highly cationic polyethylenimine, were evaluated. When the in vitro antiviral effects of SP-012 were assessed, this compound showed potent activity against HSV-1 and HSV-2. It inhibited the attachment of HSV-2 to host cells and cell-to-cell spread of infection in a concentration-dependent manner and exerted a virucidal effect. No SP-012-resistant HSV-2 was found when the virus was successively passaged in the presence of SP-012. In a mouse genital herpes model, topically administered SP-012 inhibited the progression of the disease caused by HSV infection. These data illustrate that SP-012 may be a novel class of HSV inhibitor that would be acceptable for long-term topical application.

The AGMA1 poly(amidoamine) inhibits the infectivity of herpes simplex virus in cell lines, in human cervicovaginal histocultures, and in vaginally infected mice

“…Further, clinical relapse in the latter group was milder and transient suggesting that AGMA1 reduces the number of latently infected cells and the potential for virus reactivation. In all, in vivo tests indicate that AGMA1 provides significant protection against HSV infection and disease and compares favorably well with dendrimers and polyanions considered good candidate topical microbicides [18e21, 34,58,75,76].…”

Enhanced antibacterial effect by antibiotic loaded starch nanoparticle

“…Through these observations, we can say that multiple antibiotics encapsulated single type nanoparticle can inhibit the growth of different bacteria and increase the effects. Based on the present results, SNP can be the choices of nanoparticles to encapsulate antibiotic/drug or immobilize important biomarkers and the current study may also be mimicked for other potential biomolecules such as industrially important enzymes or aptamer or other biomolecules (Poongodi et al, 2002;Anbu et al, 2006;Hayashi et al, 2014;Chen et al, 2014Chen et al, , 2015Tan et al, 2015;Azhdarzadeh et al, 2016;Phang et al, 2016;Soo et al, 2016) toward downstream applications. Previously, Mohan Yallapu et al (2012) have revealed the drug loading on different nanoparticles and shown cellulose nanoparticle has higher efficiency to load the curcumin to prevent prostate cancer.…”

Antiviral Polymers: Past Approaches and Future Possibilities

“…Other polymers have been synthesized that do not require sulfate groups to effectively inhibit HSV infection. Polymers with a polycationic character have been widely studied in the field: polylysine, polyarginine, polyacrylates, viologen (4,4′-bipyridinium salts) dendrimers, polyethylenimine, poly­(amidoamine)­s, poly­(ethylene glycol)- block -poly­(3-(methacryloyl­amino)­propyl trimethyl­ammonium chloride), and oligoamines conjugated to dextran as well as other cationic dextran derivatives. ,− Possible mechanisms of action include destabilizing cell membranes, electrostatically interacting with the envelope of lipid-enveloped viruses, or inhibiting virus–cell surface interactions by binding to negatively charged cell surface heparan sulfate. ,, In some instances, such as AGMA1 poly­(amidoamine)­s or Eudragit E100, these polymers could potentially be applied as microbicides. , …”