Vulvovaginal candidiasis (VVC) is caused mainly by opportunistic fungus Candida albicans and its yeast to hyphae transition is considered the major virulence factor of this pathogen. The increased incidence of VVC has highlighted the importance of developing new therapeutic strategies. The objective of this study was to develop a mucoadhesive nanostructured system comprising miconazole, and farnesol within chitosan for the treatment of VVC. The drug showed the antifungal miconazole expected efficacy with minimal inhibitory concentration (MIC) of 1 μg/mL. The farnesol quorum-sensing molecule was capable of inhibiting hypha-transition yeast at levels greater or equal to 300 μM. When tested together, farnesol has no effect compared to the MIC obtained for miconazole. Nanoparticles of chitosan-containing miconazole and farnesol were prepared by ionic gelation and showed favorable characteristics for use on mucous membranes, such as diameter less than 300 nanometers (nm), polydispersion index (PDI) less than 0.3, positive zeta potential and acid pH. The encapsulation efficiency (EE) of the nanoparticles was on average 81.1% for miconazole, 31.9% farnesol and 32.7% and 70.0% for miconazole and farnesol when co-encapsulated, respectively. The nanoparticles showed instability as the diameter and PDI, but were stable compared to the EE. Regarding toxicity in cultured fibroblasts (Balb/ c 3T3) were considered non-toxic. The nanoparticles showed antifungal activity against C. albicans strain used, with MIC of 2.5 μg/mL and 2 μg/mL for nanoparticles with miconazole and miconazole/ farnesol, respectively. Nanoparticles containing farnesol inhibit yeast-hyphae transition at concentrations greater than or equal to 240 uM. The antifungal activity in vivo was assessed in the murine model for VVC. Although there is no statistically significant difference between treatments in relation to the counting of colony forming units (CFU), the results suggest that chitosan nanoparticles containing miconazole and farnesol were effective for inhibiting fungal proliferation and chitosan nanoparticles containing farnesol were capable of decreasing the pathogenicity of infection demonstrated by the absence of inflammation.

Candidiasis is a serious health problem that affects a large number of people arround the world. The treatment of this disease is carried out with antifungals, which do not provide an effective cure, besides having resistance reports and high toxicity. In this context, it is necessary to study new antifungal compounds. In addition, the delivery form of the compounds in the living organism is also target of research, since the controlled release of compounds in biological systems can improve the mode of action of many drugs. Therefore, nanostructured systems, such as nanoparticles of chitosan, have been widely studied as controlled delivery of drugs. Then, this study aimed to evaluate the antifungal potential against Candida albicans of thiosemicarbazide (TSC), thiosemicarbazide-camphene (TSC-C) and chitosan nanoparticles incorporated with thiosemicarbazide (nanoTSC). In in vitro assays, the compounds were effective to inhibit nearly 100% of the fungus in concentrations of 1,37 mM to TSC, 0,02 mM to TSC-C and 0,27 mM to nanoTSC, and the most effective compound was TSC-C. NanoTSC and empty nanoparticles were also evaluated as to cell toxicity, and the concentration able to inhibit the fungus showed no cytotoxic activity. To confirm the values observed in in vitro assays, experiments were conducted using an animal model for vulvovaginal candidiasis. The results showed that TSC-C was more efficient in inhibiting C. albicans compared with TSC and nanoTSC, but was less effective than miconazole. However, histopathological analysis showed that the groups treated with the compounds under study, showed less intensity of damage to the vaginal epithelium and inflammatory infiltrates, compared with the positive control and the group treated with miconazole. Thus, the results suggest that TSC, nanoTSC and TSC-C are promising compounds in the treatment of vulvovaginal candidiasis.

This document contains the internship report carried out in Community Pharmacy under the guidance of Dr. Isabel Belchior and the Monograph with the theme "Contribution of Phytotherapy in Candida albicans infections" under the guidance of Professor António Paranhos.In the internship report, in order to make my experience in community pharmacy known, I have drawn up a SWOT analysis in which I set out the strengths, weaknesses, threats and opportunities I felt during this experience, as well as 5 practical cases I experienced during my consultations.Later on, I'll address the subject of my monograph, the abstract of which can be found below:"It is estimated that around 75% of women of childbearing age have at least one occurrence of candidiasis in their lifetime, and around 40% of them suffer a second infection. Although this infection is not life-threatening, an unresolved infection affects women's quality of life, from their social and professional lives to their mental health and sexual relations. The growing incidence of antifungal resistance, the great difficulty in treating resistant biofilms and the limitation and toxicity of existing therapies make it urgent to find new therapeutic solutions that are more tolerable, more accessible and improve patients' quality of life, with phytotherapy emerging as an alternative. This monograph is therefore a literature review on phytotherapeutic alternatives in the treatment of vulvovaginal candidiasis. Various topics are covered in this document, including some characteristics of Candida spp. and the vaginal microflora, epidemiology, symptoms and clinical manifestations, conventional therapy and phytotherapeutic alternatives to it or with potential in the development of future treatments."

No processo de formação de um futuro farmacêutico a realização de estágio numa das áreas de atuação das Ciências Farmacêuticas é extrema importância. No capítulo 1 descrevo e avalio o meu período de estágio sob a forma de uma análise SWOT, que avalia internamente os pontos fortes e fracos, e externamente as oportunidades e ameaças desta experiência. Finalmente, apresento alguns casos práticos que me surgiram durante o estágio, onde pude aplicar os conhecimentos adquiridos ao longo do curso e do estágio em contexto de atendimento ao utente. No capítulo 2 será apresentada a monografia intitulada “O uso de probióticos na prevenção e tratamento de vaginoses bacterianas e candidíases vaginais. O papel do farmacêutico comunitário”. Esta monografia aborda o tema das infeções vaginais mais comuns em contexto de farmácia comunitária e apresenta os probióticos como alternativa terapêutica, mostrando a evidência que existe no seu uso e as principais vantagens. As vaginites são uma condição clínica muito frequente na população, principalmente em mulheres na idade fértil. Um microbioma vaginal saudável é dominado por bactérias que produzem ácido láctico e componentes antimicrobianos, mantendo assim o pH vaginal baixo e conferindo proteção contra infeções. Os Lactobacilos são os microrganismos mais frequentemente isolados de uma vagina humana saudável. A disrupção do ecossistema vaginal contribui para o aumento do número de bactérias patogénicas e permite o desenvolvimento de infeções vaginais como a vaginose bacteriana (VB) ou a candidíase vulvovaginal (CVV). O uso de probióticos no tratamento de infeções vaginais comuns tem demonstrado um significante efeito a curto prazo. Estes apresentam efeitos benéficos na manutenção e no restabelecimento da microbiota vaginal saudável. Assim sendo, os probióticos podem ser aconselhados, como alternativa terapêutica, em situações de infeções vaginais ou vaginites de outra etiologia, aquando do aconselhamento farmacêutico em Farmácia Comunitária.

INTRODUÇÃO: Leveduras do gênero Candida são patógenos oportunistas freqüentemente isolados das superfícies mucosas de indivíduos normais, mas podem levar ao desenvolvimento de infecções denominadas candidíases, que variam desde lesões superficiais até infecções disseminadas. OBJETIVOS: Ampliar os conhecimentos sobre candidíase vulvovaginal (CVV: infecção de vulva e vagina, causada por leveduras comensais que habitam a mucosa vaginal) e candidíase vulvovaginal recorrente (CVVR: ocorrência de quatro ou mais episódios de CVV no período de 12 meses), bem como caracterizar e abordar o ponto de vista das influências do hospedeiro e dos fatores de virulência dos agentes causais da infecção, principalmente C. albicans, visando identificar a sua importância nessa patologia. Tanto fatores predisponentes locais como sistêmicos do hospedeiro podem contribuir para a invasão por Candida sp. Sua intensa multiplicação no canal vaginal é favorecida por uma série de fatores predisponentes abordados nesta revisão. Também tem sido postulado que existem diferenças na patogenicidade de isolados de Candida sp., não sendo o fungo apenas um participante passivo no processo infeccioso; com isso vários fatores de virulência têm sido propostos e são descritos. DISCUSSÃO E CONCLUSÕES: Este artigo de revisão bibliográfica buscou atualizar os profissionais da área da saúde em relação a CVV, CVVR, aspectos predisponentes do hospedeiro e virulência dos agentes causais, que são pouco conhecidos. Assim, a atualização e o conhecimento de conceitos básicos e clínicos relacionados com essa patologia são muito importantes para auxiliar o seu manejo pelos profissionais da área.