RESUMO
Paracoccidioidomycosis (PCM) is a granulomatous fungal disease caused by the dimorphic fungal species of Paracoccidioides, which mainly affects the lungs. Modern strategies for the treatment and/or prevention of PCM are based on a Th1-type immune response, which is important for controlling the disease. One of the most studied candidates for a vaccine is the P10 peptide, derived from the 43 kDa glycoprotein of Paracoccidioides brasiliensis. In order to improve its immune modulatory effect, the P10 peptide was associated with a chitosan-conjugated nanoparticle. The nanoparticles presented 220 nm medium size, poly dispersion index (PDI) below 0.5, zeta potential of +20 mV and encapsulation efficiency around 90%. The nanoparticles' non-toxicity was verified by hemolytic test and cell viability using murine macrophages. The nanoparticles were stable and presented physicochemical characteristics desirable for biological applications, reducing the fungal load and the usual standard concentration of the peptide from 4 to 20 times.
RESUMO
Wound healing in diabetic patients remains a worldwide problem that can cause amputations and even lead to death. This work aimed to produce lecithin-chitosan nanoparticles loaded with melatonin (MEL-NP) incorporated in a topical formulation to be evaluated for healing in the in vivo animal model for diabetes. To produce nanoparticles, an ethanolic solution containing soybean lecithin and melatonin was added dropwise to an aqueous solution of chitosan under sonication. The nanoparticles were physicochemical characterized and evaluated in vivo for toxicity using the Galleria mellonella model and its potential for wound healing in diabetic rats. The MEL-NPs presented a particle size of 160 nm and a zeta potential of 25 mV. The melatonin entrapment efficiency was 27%. Our results indicated that treatment with MEL-NP improved wound healing demonstrated by wound closure earlier than the other treatments evaluated. A desired therapeutic effect was achieved by MEL-NP in the induction of fibroblast and angiogenic proliferation. In addition, it was accompanied by an expressive collagen deposition. Considering the observed data, the MEL-NP developed could be used as a proof of concept to develop a promising strategy for the healing of diabetic wound.
Assuntos
Quitosana/química , Portadores de Fármacos/química , Lecitinas/química , Melatonina/administração & dosagem , Nanopartículas/química , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Biópsia , Diabetes Mellitus Experimental , Liberação Controlada de Fármacos , Fibroblastos , Melatonina/farmacologia , Tamanho da Partícula , Ratos , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/etiologia , Úlcera Cutânea/metabolismo , Úlcera Cutânea/patologiaRESUMO
Vulvovaginal candidiasis (VVC) is caused mainly by the opportunistic fungus Candida albicans, and its yeast to hyphae transition is considered a major virulence factor. Farnesol is a molecule that inhibits yeast to hyphae transition. The increased incidence of VVC has influenced a need for developing new therapeutic strategies. The objective was to develop a mucoadhesive nanostructured system composed of miconazole and farnesol co-encapsulated within chitosan nanoparticles. The miconazole presented a minimal inhibitory concentration (MIC) of 1 µg/ml against C. albicans. The farnesol was capable of inhibiting yeast to hyphae transition at levels greater or equal to 300 µM. The combination of miconazole and farnesol showed no change in miconazole MIC. Chitosan nanoparticles containing miconazole and farnesol were prepared by ionic gelation and showed favorable characteristics for use on mucous membranes. They showed size variation and polydispersion index (PDI) after 30 days, but the efficiency of drug encapsulation was maintained. Regarding toxicity in cultured fibroblasts (BALB/c 3T3) the nanoparticles were considered nontoxic. The nanoparticles showed antifungal activity against the C. albicans strain used with MICs of 2.5 µg/ml and 2 µg/ml for nanoparticles containing miconazole or miconazole/farnesol, respectively. Nanoparticles containing farnesol inhibited yeast to hyphae transition at concentrations greater than or equal to 240 µM. The in vivo antifungal activity was assessed in the murine model for VVC. The results suggested that chitosan nanoparticles containing miconazole and farnesol were effective at inhibiting fungal proliferation. Additionally, chitosan nanoparticles containing farnesol were capable of decreasing the pathogenicity of infection, demonstrated through the absence of inflammation.