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.
Trans-resveratrol (RSV) is a natural compound with several properties, such as the ability to inhibit the tyrosinase enzyme, with potential application as a skin-lightning agent and for the treatment of skin disorders associated with hyperpigmentation and melanogenesis. However, the drug faces several drawbacks which altogether limit its therapeutic application. Thus, drug loading into nanocarriers emerge as an alternative to circumvent these problems. Herein, nanostructured lipid carriers (NLCs) have been employed for RSV encapsulation, with comparison of two different lipids, glyceryl behenate (more hydrophobic), and polyoxyethylene 40 (PEG 40) stearate. PEG 40 stearate-containing NLCs presented smaller particle size and polydispersity compared with glyceryl behenate, attributed to better emulsification and nanoparticle formation, resulting in higher RSV encapsulation efficiency. Drug was loaded in both carriers as a molecular dispersion. Furthermore, the formulations had very low RSV release, which occurred due to the crystallinity degree of lipid matrix, in accordance with the DSC data. Moreover, RSV cytotoxicity against L-929 cells was not increased when loaded into nanocarriers. Interestingly, RSV-loaded formulation prepared with PEG-40 stearate resulted on greater tyrosinase inhibition than RSV solution and formulation containing glyceryl behenate, equivalent to 1.31 and 1.83 times higher, respectively, demonstrating that the incorporation of RSV into NLC allowed an enhanced tyrosinase inhibitory activity. Overall, the results obtained herein evidence potential for future in vivo evaluation of RSV-loaded NLCs.
Breast cancer is a serious public health problem that causes thousands of deaths annually. Chemotherapy continues to play a central role in the management of breast cancer but is associated with extreme off-target toxicity. Therefore, treatments that directly target the tumor and display reduced susceptibility to resistance could improve the outcome and quality of life for patients suffering from this disease. Photodynamic therapy is a targeted treatment based on the use of light to activate a photosensitizer (PS) that then interacts with molecular oxygen and other biochemical substrates to generate cytotoxic levels of Reactive Oxygen Species. Currently approved PS also tends to have poor aqueous solubility that can cause problems when delivered intravenously. In order to circumvent this limitation, in this manuscript, we evaluate the potential of a phthalocyanine-loaded nanostructured lipid carrier (NLC) functionalized with folic acid (FA). To prepare the FA labelled NLC, the polymer PF127 was first esterified with FA and emulsified with an oil phase containing polyoxyethylene 40 stearate, capric/caprylic acid triglycerides, ethoxylated hydrogenated castor oil 40 and the PS zinc phthalocyanine. The resulting PS loaded FA-NLC had a hydrodynamic diameter of 180 nm and were stable in suspension for > 90 days. Interestingly, the amount of singlet oxygen generated upon light activation for the PS loaded FA-NLC was substantially higher than the free PS, yet at a lower PS concentration. The PS was released from the NLC in a sustained manner with 4.13 ± 0.58% and 27.7 ± 3.16% after 30 min and 7 days, respectively. Finally, cytotoxicity assays showed that NLC in the concentrations of 09.1 μM of PS present non-toxic with > 80 ± 6.8% viable and after 90 s of the light-exposed the results show a statistically significant decrease in cell viability (57 ± 4%). The results obtained allow us to conclude that the functionalized NLC incorporated with PS associated with the PDT technique have characteristics that make them potential candidates for the alternative treatment of breast cancer.
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