Lactobacillus crispatus BC1 Biosurfactant Delivered by Hyalurosomes: An Advanced Strategy to Counteract Candida Biofilm

Abstract

The emergence of resistance to antifungal drugs has made the treatment of vulvovaginal candidiasis (VVC) very challenging. Among natural substances, biosurfactants (BS) produced by Lactobacillus have gained increasing interest in counteracting Candida infections for their proven anti-adhesive properties and safety profile. In the present study, liposomes (LP-BS) or liposomes coated with hyaluronic acid (HY-LP-BS) were prepared in the presence of the BS isolated from the vaginal strain Lactobacillus crispatus BC1 and characterized in terms of size, ζ potential, stability and mucoadhesion. The anti-biofilm activity of free BS, LP-BS and HY-LP-BS was investigated against different Candida albicans and non-albicans strains (C. glabrata, C. lusitaniae, C. tropicalis, C. krusei and C. parapsilosis), clinically isolated from patients affected by VVC. The inhibition of biofilm formation and the dispersal of pre-formed biofilm were evaluated. The obtained phospholipid vesicles showed suitable size for vaginal application and good stability over the storage period. HY-LP-BS exhibited good mucoadhesive properties and the best anti-biofilm profile, both in preventing or limiting the surface colonization by a broad spectrum of Candida species. In conclusion, the formulation of a novel antifungal agent derived from the vaginal microbiota into mucoadhesive nanocarriers appears to be a promising biotherapeutic strategy to counteract vulvovaginal candidiasis.

Keywords: Candida; Lactobacillus; biofilm; biosurfactant; hyalurosomes; liposomes; mucoadhesion.

Figure 1

Variation of size of liposomes (LP) and hyalurosomes (HY-LP) with and without biosurfactants (BS) during 180 days of storage at 4–8 °C (mean ± SD, n = 3).

Figure 2

Absorbance at 650 nm measured for formulations incubated or not in the presence of mucin (mean ± SD, n = 3). The statistical significance with respect to formulation in absence of mucin was reported, *: p < 0.05.

Figure 3

Anti-biofilm activity: inhibition of the development of (a) C. albicans and (b) non-albicans biofilms. Results are expressed as inhibition percentage (mean ± SD, n = 5). The statistical significance with respect to untreated control was reported, §: p < 0.01. Statistical differences between BS, LP-BS and HY-LP-BS were also calculated, *: p < 0.05.

Figure 4

Anti-biofilm activity: dispersal of pre-formed (a) C. albicans and (b) non-albicans biofilms. Results are expressed as eradication percentage (mean ± SD, n = 5). The statistical significance with respect to untreated control was reported, §: p < 0.01. Statistical differences between BS, LP-BS and HY-LP-BS were also calculated, *: p < 0.05.