Sexually transmitted infection (STI) prevention is an important reason for condom use. However, a condom does not offer complete protection against HIV-1, HSV-2, human papilloma virus, or bacterial and fungal sexual infections in both men and women.24
The nonoxynol-9-coated condom was once believed to offer additional protection against STIs. However, recent studies have shown that the use of nonoxynol-9-coated condoms induces inflammation and ulceration to genital mucosa, thereby increasing the probability of transmitted infectious agents.25
Till now there has been no single condom with additional protection against sexually transmitted infections available on the market. Previous studies have shown that Ag-NPs exhibit anti-inflammatory effect,27
a broad spectrum of antibacterial and antiviral activities, and are relatively nontoxic to the human body at low concentration.12
Thus, in this study, we have developed an Ag-NPs-coated condom product and further tested its inhibitory activities against HIV-1, HSV-1/2, and other bacterial and fungal pathogens.
The spectroscopic analyses of the silver Ag-NPs-coated PUC showed a peak at 430 nm, which is due to excitation of the surface plasmon resonance of Ag-NPs () and optical absorption peak in the EDAX at 3 keV clearly confirmed the presence of nanocrystalline elemental silver.22
The FTIR analysis shows most of the functional group of polyurethane remained intact after coating with Ag-NPs (). Thus, this method preserves the original qualities of the manufactured condom. Importantly, coating takes place on both the inner and outer surfaces of the condom, thus providing a double protection against pathogens.
Prior to testing its antimicrobial efficacy, an evaluation of whether the contact of the Ag-NPs-coated PUC on human cells would cause any detrimental effect was required. Our results indicate that the Ag-NPs-coated PUC did not significantly affect HeLa cells, 293 T, and C8166 T cells’ survival and growth after the cells made contact with the Ag-NPs-coated PUC for up to 3 hours (). However, whether contact with the Ag-NPs-coated PUC for a longer time would result in cell damage requires further investigation. Notably, Lara et al demonstrated that a high concentration of polyvinyl pyrolidone-coated Ag-NPs (0.6 mg/mL) were only cytotoxic to a small population of cells, affecting the viability of 20% of the cells in the cervical explants.30
In addition, our data show that Ag-NPs were stably bound to the polyurethane condom and were not significantly leached from the condom due to the interaction of the Ag-NPs with the nitrogen atom of the PUC. This feature could provide additional advantage for the product used at the mucosal surface since the Ag-NPs will be removed with the PUC after use.
Previous studies have proven that Ag-NPs are a broad-spectrum biocide.31
However, whether Ag-NPs chemically bound to the condom still possess a potent activity against HIV and other sexually transmitted pathogens is unclear. In this study, we have clearly shown that the contact of the Ag-NPs-coated PUC with both T-tropic and macrophage-tropic HIV-1 could efficiently inactivate the virus infectivity. Such potent anti-HIV activity was mediated by Ag-NPs that are bound to the PUC, but not the PUC itself since the PUC alone did not show any inhibitory effect (). Another possibility could be that the Ag-NPs associated with the condom could be released into the medium after extensive shaking in the medium, and these released Ag-NPs could be the molecules acting on HIV-1 virions. To verify this question, we have extensively shaken the Ag-NPs-coated PUC in the medium for 30 minutes and collected the supernatant. Infection analysis revealed that the collected supernatant only showed a modest anti-HIV effect. This effect may be due to the fact that the culture medium contains different kind of ions, which may influence the small amount of silver ions released from the condom. However, the majority of anti-HIV activity was still associated with the Ag-NPs associated with the PUC (). All of these results indicate that Ag-NPs were tightly bound to the PUC and these bound Ag-NPs were biologically active and are able to efficiently inactivate HIV-1 infectiousness. It is known that HIV-1 strains found in humans can differ widely in their pathogenicity, virulence, and sensitivity to particular antiviral drugs.32
Thus, it is necessary in our continuing study to further test whether the Ag-NPs-coated PUC could have an effective broad spectrum activity against different clades of HIV-1 as well as various drug-resistant viruses. In addition, it is interesting to explore the possible mechanism of how PUC-bound Ag-NPs achieve such potent anti-HIV activity. One possible mechanism could be due to the direct transfer of silver ions from oxidized NPs to biological targets such as virus membrane proteins, like gp120 and gp41. Also, it should be noted that a very small amount of silver ions could also be released from the Ag-NPs-coated PUC () and it is possible that these very low levels of silver ions at the mucosal surface would enhance the anti-HIV efficiency during and even after the use of the Ag-NPs-coated PUC. More detailed studies will address these questions.
Herpes simplex virus (HSV) is another common infectious agent that occurs worldwide and infects humans of all ages.12
The outcome of HSV-1 infection includes a wide variety of clinical manifestations, ranging from asymptomatic infection to oral cold sores and severe encephalitis while HSV-2 causes genital herpes. Over the last decade, due to the growth of immunocompromised patients and an occurrence of HIV infection, an increase in the number of HSV infections and its severity has been reported.33
Also, numerous observational data suggest that HSV-2 genital infection facilitates HIV acquisition through genital tract mucosa.34
Therefore, it is interesting to test whether the Ag-NPs-coated PUC could also disrupt HSV infectivity. Indeed, the results presented in the study clearly showed that contact of the Ag-NPs-coated PUC to both HSV-1 and HSV-2 was able to efficiently inactivate their infectivity in Vero E6 cells (). This indicates that, in addition to inhibiting HIV-1, the Ag-NPs-coated PUC is also efficient to prevent HSV-1/2 infection.
Of interest, the antibacterial and antifungal activity of the Ag-NPs-coated PUC was also observed in the study (). It is believed that the antibacterial and antifungal activities of Ag-NPs are the result of the disruption of energy metabolism, electrolyte-transport systems, and/or distortion of bacterial cell wall. This disruption is due to the binding of Ag-NPs with bacterial sulphydryl- or histidyl-containing proteins.23
Recently, a study has shown that Ag-NPs arrested the cell cycle at the G2/M phase in C. albicans
and also inhibited the budding process, probably through the destruction of membrane integrity.11
Obviously, more detailed investigation of the molecular mechanisms underlying the broad antibacterial and antifungal activity of the Ag-NPs-coated PUC will be necessary and will facilitate our better understanding of the broad actions of the Ag-NPs-coated PUC.