Curcumin-Loaded Liquid Crystalline Systems for Controlled Drug Release and Improved Treatment of Vulvovaginal Candidiasis

Abstract

Vulvovaginal candidiasis (VVC) is the most common infection caused by Candida albicans and greatly reduces the quality of life of women affected by it. Due to the ineffectiveness of conventional treatments, there is growing interest in research involving compounds of natural origin. One such compound is curcumin (CUR), which has been proven to be effective against this microorganism. However, some of CUR's physicochemical properties, especially its low aqueous solubility, make the therapeutic application of this compound difficult. Thus, the incorporation of CUR in mucoadhesive liquid crystalline systems (MLCSs) for vaginal administration may be an efficient strategy for the treatment of VVC. MLCSs are capable of potentiating the compound's action, releasing it in a controlled manner, and can enable longer exposure at the site of infection. In this study, MLCSs consisting of oleic acid and ergosterol 5:1 (w/w) as the oily phase, PPG-5-CETETH-20 as the surfactant, and a polymer dispersion of 1% chitosan as the aqueous phase, were developed for the application of CUR (MLCS-CUR) in VVC treatment. The formulations were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), oscillatory rheometry, continuous shear rheometry, texture profile analysis, and in vitro mucoadhesion. In addition, the antimicrobial activity was evaluated in vitro, and the effects on local fungal burden and cytokine profiles were investigated in a murine model of VVC. PLM and SAXS showed that the developed formulations presented a characteristic of a microemulsion. However, after the addition of artificial vaginal mucus (AVM), PLM showed that the formulations had structures similar to the "Maltese cross" characteristic of lamellar MLCS. Mucoadhesive test results showed an increase in the mucoadhesive strength of these formulations. Rheology analyses suggested long-lasting action of the formulation at the infected site. The in vitro antimicrobial activity assays suggested that CUR possesses antifungal activity against Candida albicans, determined after its incorporation into the MLCS. Further, MLCS-CUR was also more effective in vivo in the control of vaginal infection than treatment with fluconazole. Immunological assays showed that the ratio of pro-inflammatory (IL-1β) to anti-inflammatory (TGF-β) cytokines has decreased and that there is a reduction in the number of polymorphonuclear neutrophils recruited to the vaginal lumen, showing that treatment with MLCS-CUR was effective in modulating the inflammatory reaction associated with the infection. The results suggest that MLCSs could potentially be used in the treatment of VVC with CUR.

Nanocarriers Provide Sustained Antifungal Activity for Amphotericin B and Miltefosine in the Topical Treatment of Murine Vaginal Candidiasis

“…The advantage of the microemulsion used here compared to the alginate-based nanoparticle is the in situ (i.e., in the vaginal mucosa) formation of a liquid crystalline system with a gellike appearance upon contact with water (Geraghty et al, 1996;Lopes et al, 2006;Phelps et al, 2011). The gel formed after ME swelling is more viscous, which improves the residence time in the vaginal canal (Geraghty et al, 1997;Rodero et al, 2018;Jie et al, 2019). Advantages resulting from this property include the lower probability of leaking after delivery and the possibility of reducing the dosing frequency compared to less viscous systems (Rodero et al, 2018;Jie et al, 2019).…”

“…The gel formed after ME swelling is more viscous, which improves the residence time in the vaginal canal (Geraghty et al, 1997;Rodero et al, 2018;Jie et al, 2019). Advantages resulting from this property include the lower probability of leaking after delivery and the possibility of reducing the dosing frequency compared to less viscous systems (Rodero et al, 2018;Jie et al, 2019). Thus, the fluid ME can be considered a ready-to-use delivery system and does not need to be incorporated in a gel or in any other dosage form for administration since it spontaneously forms a gel in situ.…”

Applying the Host-Microbe Damage Response Framework to Candida Pathogenesis: Current and Prospective Strategies to Reduce Damage

“…Other approaches include probiotics (e.g., Lactobacillus spp. ), or synthetic or natural-based compounds (e.g., polyphenols) that have been shown to have anti-inflammatory effects [184][185][186][187][188][189]. On the other hand, strategies to restore PMN antifungal activity during vaginitis by targeting HS would conceivably reduce the organism burden with a functional PMN response and ultimately restore the asymptomatic state.…”

Development and Evaluation of Curcumin Liquid Crystal Systems for Cervical Cancer

“…Recently, various targeted drug delivery systems have received attention for their ability of delivering drugs to cancer tissues in a highly selective manner without affecting other tissues. Such systems include nanoparticles [8], nanostructured lipid particles [9], liquid crystals (LC) [10], pH-responsive micelles [11], etc. LC have the ability to form an organized mesophase exhibiting both crystalline solid and liquid properties [12].…”

“…The inhibition rate of curcumin was found to be 74.33% [4,5]. Rodero et al reported that curcumin-loaded liquid crystalline systems with additional mucoadhesive properties are an efficient means of treating vulvovaginal candidiasis (VVC) upon vaginal administration [10]. Likewise, an in vitro study by Salmazi et al (2015) showed better potency of a curcumin-loaded LC precursor mucoadhesive system consisting of chitosan and poloxamer 407 compared with a curcumin solution against VVC [19].…”