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- Innovative therapeutic strategies for the treatment of vaginal infectionsPublication . Tomás, Mariana Isabel Cabral; Oliveira, José António Martinez Souto de; Oliveira, Rita Manuela Palmeira deBacterial vaginosis (BV) and vulvovaginal candidosis (VVC) are the most prevalent vaginal infections, both affecting many women, with negative impact on their self-esteem and being associated with huge discomfort and changes in daily routines, especially the sexual life. VVC is predominantly caused by Candida albicans, which is considered an opportunistic pathogen, but other Candida species such as C. glabrata, C. krusei, C. tropicalis and C. parapsilosis can also be etiological agents. The most common symptoms associated with VVC are vaginal irritation, vulvar burning, pruritus, swelling and discharge with vaginal fluid usually described as “cottage cheese-like”. For the treatment VVC, standard treatment is presently based on azoles (single dose of fluconazole 150mg or Itraconazole 200 mg twice daily for one day or short-course topical formulations, such as clotrimazole cream or clotrimazole vaginal tablet 500 mg). Nevertheless, 5–8% of women of reproductive age are affected by recurrent episodes of vulvovaginal candidosis (cVVC), defined by three or more episodes occurring in a 12 months period, as a result of resistance to azoles, particularly in Non albicans Candida species cases, or re-infection. Although some women are asymptomatic, most women with of BV, experiences an unpleasant thin vaginal malodorous discharge. This clinical condition is considered to be a dysbiosis, that is the replacement of saprophytic vaginal flora, dominated by Lactobacillus spp. by dense, structured and polymicrobial biofilm primarily constituted by Gardnerella vaginalis. For the treatment of BV, international guidelines recommend the administration of metronidazole, clindamycin or tinidazole orally or intravaginally as the standard treatment. However, the treatment with these antibiotics is associated with high levels of failure and recurrence rates. These may be associated with antibiotic resistance, the inability to eradicate the polymicrobial biofilms, and failure to re-establish acidic pH and the Lactobacillus-dominated commensal flora. The aim of this work was to develop and characterize new therapeutic approaches for the treatment of vaginal infections. Specifically, we aimed to design two effective and safe products with potential to be transferred to the pharmaceutical industry: a bioadhesive sodium bicarbonate gel for the treatment of VVC and a vaginal sheet with Thymbra capitata essential oil (EO) for the treatment of BV. Bacterial vaginosis (BV) and vulvovaginal candidosis (VVC) are the most prevalent vaginal infections, both affecting many women, with negative impact on their self-esteem and being associated with huge discomfort and changes in daily routines, especially the sexual life. VVC is predominantly caused by Candida albicans, which is considered an opportunistic pathogen, but other Candida species such as C. glabrata, C. krusei, C. tropicalis and C. parapsilosis can also be etiological agents. The most common symptoms associated with VVC are vaginal irritation, vulvar burning, pruritus, swelling and discharge with vaginal fluid usually described as “cottage cheese-like”. For the treatment VVC, standard treatment is presently based on azoles (single dose of fluconazole 150mg or Itraconazole 200 mg twice daily for one day or short-course topical formulations, such as clotrimazole cream or clotrimazole vaginal tablet 500 mg). Nevertheless, 5–8% of women of reproductive age are affected by recurrent episodes of vulvovaginal candidosis (cVVC), defined by three or more episodes occurring in a 12 months period, as a result of resistance to azoles, particularly in Non albicans Candida species cases, or re-infection. Although some women are asymptomatic, most women with of BV, experiences an unpleasant thin vaginal malodorous discharge. This clinical condition is considered to be a dysbiosis, that is the replacement of saprophytic vaginal flora, dominated by Lactobacillus spp. by dense, structured and polymicrobial biofilm primarily constituted by Gardnerella vaginalis. For the treatment of BV, international guidelines recommend the administration of metronidazole, clindamycin or tinidazole orally or intravaginally as the standard treatment. However, the treatment with these antibiotics is associated with high levels of failure and recurrence rates. These may be associated with antibiotic resistance, the inability to eradicate the polymicrobial biofilms, and failure to re-establish acidic pH and the Lactobacillus-dominated commensal flora. The aim of this work was to develop and characterize new therapeutic approaches for the treatment of vaginal infections. Specifically, we aimed to design two effective and safe products with potential to be transferred to the pharmaceutical industry: a bioadhesive sodium bicarbonate gel for the treatment of VVC and a vaginal sheet with Thymbra capitata essential oil (EO) for the treatment of BV. it is designed to be used for short periods. Vaginal sheet D.O diluted at 10% w/v was biocompatible in model tissue. Concluding: two products with potential to be transferred from academy to industrial pharmacy were designed for the treatment of two common vaginal infections. A sodium bicarbonate gel and a vaginal sheet with T. capitata EO were developed to respond to the clinical requirements but also to women’s preferences, overcoming disadvantages associated with conventional dosage forms. Although the present results are promising in terms of predictable acceptability, in vivo technological performance, efficacy and safety, more complete studies are needed in a pre-clinical phase and finally clinical assays will for confirm their usefulness.
- Estudo da influência de fatores de formulação no doseamento e estabilidade de isotiazolinonas em champôsPublication . Tomás, Mariana Isabel Cabral; Oliveira, Rita Manuela Palmeira de; Ferreira, SofiaA minha experiencia profissionalizante para a obtenção do grau de mestre em Ciências Farmacêuticas englobou três vertentes: investigação laboratorial, farmácia hospitalar e farmácia comunitária. No capítulo 1 encontra-se descrito o projeto de investigação desenvolvido que teve como objetivo o estudo da influência de fatores de formulação no e doseamento e estabilidade de isotiazolinonas em champôs. Os cosméticos são vistos como bens de primeira necessidade pela maioria da população, o que faz com que seja um mercado em constante crescimento. Por outro lado, há uma preocupação crescente com a segurança do consumidor, sendo que cada vez surgem mais restrições no que diz respeito aos conservantes autorizados, bem como aos seus limites de utilização. As isotiazolinonas são dos conservantes mais utilizados em champôs, contudo encontra-se-lhes associado um potencial de indução de dermatite de contacto, o que torna essencial o cumprimento dos limites legalmente definidos. Os champôs são misturas complexas com vários ingredientes adicionados, o que potencia a interação destes conservantes com outras substâncias presentes nas formulações e dificulta o seu doseamento. Neste estudo, desenvolveram-se duas formulações base de champô, contendo uma mistura de 5-cloro-2-metil-4-isotiazolin-3-ona e 2-metil-4-isotiazolin-3-ona, às quais foram adicionadas substâncias que possivelmente interferem na estabilidade do conservante. Otimizou-se um método de extração e doseamento por cromatografia líquida de alta eficiência que permitiu o doseamento da mistura de conservante. O segundo e terceiro capítulos dizem respeito aos estágios desenvolvidos nos serviços farmacêuticos do Hospital Sousa Martins e Farmácia Holon Covilhã, respetivamente. Nestes relatórios encontra-se descrito o funcionamento dos serviços, o papel do farmacêutico e as suas, bem como os conhecimentos e competências adquiridas, essenciais para a minha formação enquanto futura farmacêutica.