Utilizing Liposomal Quercetin and Gallic Acid in Localized Treatment of Vaginal Candida Infections

Abstract

Vulvovaginal candidiasis (VVC) is a widely spread fungal infection that causes itching, pain and inflammation at the vaginal site. Although common, currently available treatment suffers from limited efficacy and high recurrence. In addition, the growing problem of resistance to azole drugs used in current treatments emphasizes the need for superior treatment options. Antimicrobial polyphenols are an attractive approach offering multitargeting therapy. We aimed to develop novel liposomes for simultaneous delivery of two polyphenols (quercetin, Q, and gallic acid, GA) that, when released within the vaginal cavity, act in synergy to eradicate infection while alleviating the symptoms of VVC. Q was selected for its anti-itching and anti-inflammatory properties, while GA for its reported activity against Candida. Novel liposomes containing only Q (LP-Q), only GA (LP-GA) or both polyphenols (LP-Q+GA) were in the size range around 200 nm. Q was efficiently entrapped in both LP-Q and in LP-Q+GA (85%) while the entrapment of GA was higher in LP-Q+GA (30%) than in LP-GA (25%). Liposomes, especially LP-Q+GA, promoted sustained release of both polyphenols. Q and GA acted in synergy, increasing the antioxidant activities of a single polyphenol. Polyphenol-liposomes were not cytotoxic and displayed stronger anti-inflammatory effects than free polyphenols. Finally, LP-GA and LP-Q+GA considerably reduced C. albicans growth.

Following the Fate of Dye-Containing Liposomes In Vitro

“…All liposomal formulations showed lipid concentration-dependent inhibition of NO production in LPS-activated macrophage ( Figure 5 ) and the results were in agreement with the literature [ 16 , 17 ]. Liposomal formulations at the concentration of 50 µg/mL inhibited approximately 50% of NO production as compared to the non-treated control.…”

“…Slight deviations (mostly not on significant level) were observed for both dye-containing liposomes when liposomes comprised higher dye to lipid ratios (T3, T4 and C3, C4, respectively). All liposomal formulations showed lipid concentration-dependent inhibition of NO production in LPS-activated macrophage ( Figure 5) and the results were in agreement with the literature [16,17]. Liposomal formulations at the concentration of 50 µg/mL inhibited approximately 50% of NO production as compared to the non-treated control.…”

“…As a second type of cells, we selected macrophages due to their role in interacting with nanocarriers and wide variety of inflammatory diseases [36]. We could not detect liposome-induced proliferative effects in non-inflamed cells ( Figure 4A), however, we confirmed a concentration-dependent reduction in NO production after liposomal treatment of LPS-inflamed cells ( Figure 5) [16,17]. Although no toxicity was determined for the dye-containing liposomes, we observed larger variability in the readings for NO production in activated macrophages.…”

The Vaginal-PVPA: A Vaginal Mucosa-Mimicking In Vitro Permeation Tool for Evaluation of Mucoadhesive Formulations

“…The use of liposomes as drug-delivery systems for vaginal administration has gained increasing attention over the past decades [17,[23][24][25] due to their biodegradability, biocompatibility, non-irritating properties towards the vaginal mucosa and to their intrinsic capacity of shielding active substances from the possible degradation occurring at the vaginal site [26]. Moreover, the coating of these formulations with chitosan can improve the mucoadhesive and antimicrobial properties of such drug-delivery systems [6,13,17], which enables higher resident time in the vagina and aids against bacterial infections.…”

Phytochemical Composition and In Vitro Antimicrobial Activity of Essential Oils from the Lamiaceae Family against Streptococcus agalactiae and Candida albicans Biofilms

“…Candida albicans is a normal constituent of human flora, and a common colonizer of mucosal membrane, skin, gastrointestinal tract, and vaginal mucosa. In more than 75% of cases, this species behaves as an opportunistic pathogen responsible for vulvovaginal candidiasis (VVC) [ 8 , 9 , 10 , 11 ]. The ability of Candida species to form biofilm is considered as a critical point in its pathogenesis, with an increased resistance to traditional antimycotic agents [ 9 , 12 , 13 , 14 ].…”