Benzoyl Peroxide Formulated Polycarbophil/Carbopol 934P Hydrogel with Selective Antimicrobial Activity, Potentially Beneficial for Treatment and Prevention of Bacterial Vaginosis

The human vagina is colonized by a variety of indigenous microflora; in healthy individuals the predominant bacterial genus is Lactobacillus while those with bacterial vaginosis (BV) carry a variety of anaerobic representatives of the phylum Actinobacteria. In this study, we evaluated the antimicrobial activity of benzoyl peroxide (BPO) encapsulated in a hydrogel against Gardnerella vaginalis, one of the causative agents of BV, as well as indicating its safety for healthy human lactobacilli. Herein, it is shown that in well diffusion assays G. vaginalis is inhibited at 0.01% hydrogel-encapsulated BPO and that the tested Lactobacillus spp. can tolerate concentrations of BPO up to 2.5%. In direct contact assays (cells grown in a liquid culture containing hydrogel with 1% BPO or BPO particles), we demonstrated that hydrogels loaded with 1% BPO caused 6-log reduction of G. vaginalis. Conversely, three of the tested Lactobacillus spp. were not inhibited while L. acidophilus growth was slightly delayed. The rheological properties of the hydrogel formulation were probed using oscillation frequency sweep, oscillation shear stress sweep, and shear rate sweep. This shows the gel to be suitable for vaginal application and that the encapsulation of BPO did not alter rheological properties. 1. Introduction The healthy human vagina is colonized by a variety of bacterial species with lactobacilli being a predominant group of microorganisms. The cause and etiopathogenesis of bacterial vaginosis (BV) is still poorly understood; however, it has been extensively shown that when the natural ecology shifts to mainly Gram-negative Actinobacteria, microbial disease such as BV can occur [1]. BV affects one in three women in the United States. Initially, infection leads to discomfort and a foul discharge while long-term infection has been correlated with increased risk of pelvic inflammatory disease, sexually transmitted infections, and pregnancy complications including preterm birth [2, 3]. Advanced methodological approaches utilizing qPCR and deep sequencing confirm BV as a multispecies infection [4, 5]. However, G. vaginalis is observed in approximately 70% of tested women regardless of whether the individual is considered positive for BV based on the Nugent criteria [5–7]. Current Food and Drug Administration (FDA) approved treatments include nitroimidazoles (i.e., metronidazole) or the lincosamide clindamycin [8]. These antibiotics alter the indigenous microflora by inhibiting both the problematic and healthy bacterial species. G. vaginalis and other anaerobic bacteria