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Authors
Abstract(s)
O vírus do Papiloma Humano, (HPV) é um dos agentes infeciosos de transmissão
sexual mais comum e é responsável por mais de 5 % de todos os cancros humanos. Dos
200 genótipos capazes de infectar os humanos, 40 podem infectar o trato anogenital e
causar lesões benignas ou pré-cancerosas. Mais de 90% de todos os casos de cancro do
colo do útero são devido a infeções causadas pelo HPV de alto risco. Na grande maioria
dos casos, as infeções provocadas pelo HPV apenas são detectadas quando as lesões já
são de elevado grau e evoluem para cancro. Embora existam vacinas profiláticas contra
o HPV, estas são ineficazes nos casos de infeção latente, não sendo deste modo
benéficas para indivíduos já infectados e com lesões causadas pelo mesmo.
Diversos sistemas de entrega de fármacos anticancerígenos com elevada especificidade
tem sido desenvolvido para o tratamento de cancro, nomeadamente lesões cancerosas
uterinas provocadas pelo HPV. O uso de formulações vaginais é frequentemente
indicado para a aplicação tópica e tem sido frequentemente utilizado no tratamento de
lesões vaginais.
Este trabalho tem como objetivo desenvolver e caracterizar formulações contendo óleo
essencial de Thymus vulgaris (TEO) na sua constituição e compostos tais como
mitoxantrona (MTX) e do derivado de laranja de acridina (C8), de forma a avaliar a sua
ação anticancerígena, nas células do cancro do colo do útero. O tomilho, para além de
propriedades antifúngicas e antibacterianas, também apresenta propriedades
anticancerígenas resultantes do aumento específico dos radicais livres e do stress
oxidativo causado nas células cancerosas.
O seu efeito antiproliferativo foi avaliado por ensaios de viabilidade celular através do
ensaio colorimétrico do reagente brometo de [3-(4,5-dimetiltiazol-2-l)-2,5-difenil
tetrazólio MTT) nas linhas celulares HeLa e NHDF. Para avaliação da permeabilidade
dos compostos no tecido vaginal da porca, foi utilizada a câmara de Ussing e posterior
quantificação pelo método da cromatografia líquida de alta eficiência (HPLC). As
formulações também foram caracterizadas quanto aos valores de pH e capacidade
tampão, osmolalidade, viscosidade e bioadesão.
Os resultados demonstraram que houve um aumento no efeito antiproliferativo das
formulações com MTX e C8 na presença de TEO, possívelmente indicando que o TEO
pode ser um potencializador do efeito antiproliferativo de MTX e C8 nas linhas celulares do cancro do colo do útero. Entretanto o TEO apresentou alguma toxicidade
tanto nas células HeLa como nas células saudáveis (NHDF), apresentando um efeito
antiproliferativo maior nas células HeLa, na maioria das formulações nas
concentrações de 1 % e 0,4 %. Os resultados da caracterização das formulações
revelaram que nem sempre apresentaram as propriedades tecnológicas ideais (pH,
capacidade de tamponamento, osmolalidade, viscosidade e bioadesão); no entanto,
obteve-se os resultados esperados com as diluições fisiológicas no fluído vaginal.
No geral, os resultados apresentados neste trabalho demonstraram que as formulações
contendo o TEO na sua constituição, principalmente a de T1% + C8 são as mais
promissoras em termos de custo-benefício e e aplicação tópica do composto ativo para
o tratamento de lesões causadas pelo HPV.
Human papillomavirus (HPV) is one of the most common sexually transmitted infectious agents being also responsible for 5% of all human cancers. More than 200 types of HPV have been recognized capable of infecting humans, more than 40 infect the genital tract. causing benign or precancerous lesions. 90% of cervical cancer cases are due to high-risk HPVs and usually is detected when HPV infection remain over long periods. Although prophylactic vaccines can prevent infections by HPV types, they are ineffective to people who are already infected with HPV, because vaccines do not treat infection. They provide maximum benefit if a person receives them before he or she is sexually active. Several types of delivery systems developed for cancer revealed high specificity to uterine cancerous lesions caused by HPV. The vaginal formulations is often indicated for the topical application of drugs and has been frequently used in the treatment of vaginal lesions. This work aims to develop and characterize formulations containing Thymus vulgaris essential oil (TEO) in its constitution and compounds mitoxantrone (MTX) and acridine orange derivative (C8) in order to evaluate its action in terms of cytotoxic effect on cervical cancer cells HeLa. Thyme have showed effective bactericidal and antifungal activities and also anticancer properties resulting from the specific increase of the free radicals and oxidative stress caused in cancer cells. The antiproliferative effect was assessed by colorimetric assay of [3- (4,5- dimethylthiazol-2-l) -2,5-diphenyl tetrazolium MTT reagent in HeLa and NHDF cell lines. The permeability of the compounds was evaluated in the Ussing chamber using vaginal tissue and quantified by the high-performance liquid chromatography (HPLC) method. The formulations were also characterized in terms of pH buffering capacity, osmolality, viscosity and bioadhesion. The TEO formulations loaded with MTX and C8 showed an increase of antiproliferative effect, indicating that TEO may be an enhancer of the cytotoxic effect of MTX and C8 in cervical cancer cell lines. However, TEO showed some toxicity in both HeLa cells and normal cells (NHDF), presenting a greater antiproliferative effect in HeLa cells, in most formulations at concentrations of 1% and 0.4%. The formulations did not present the ideal technological properties (pH, buffering capacity, osmolality, viscosity and bioadhesion); however, in dilutions of vaginal fluid simulant presented the expected results. Overall, the formulations containing thyme and T1% + C8 developed under this project are the most promising in terms of cost-benefit and topical application for the treatment of lesions caused by HPV.
Human papillomavirus (HPV) is one of the most common sexually transmitted infectious agents being also responsible for 5% of all human cancers. More than 200 types of HPV have been recognized capable of infecting humans, more than 40 infect the genital tract. causing benign or precancerous lesions. 90% of cervical cancer cases are due to high-risk HPVs and usually is detected when HPV infection remain over long periods. Although prophylactic vaccines can prevent infections by HPV types, they are ineffective to people who are already infected with HPV, because vaccines do not treat infection. They provide maximum benefit if a person receives them before he or she is sexually active. Several types of delivery systems developed for cancer revealed high specificity to uterine cancerous lesions caused by HPV. The vaginal formulations is often indicated for the topical application of drugs and has been frequently used in the treatment of vaginal lesions. This work aims to develop and characterize formulations containing Thymus vulgaris essential oil (TEO) in its constitution and compounds mitoxantrone (MTX) and acridine orange derivative (C8) in order to evaluate its action in terms of cytotoxic effect on cervical cancer cells HeLa. Thyme have showed effective bactericidal and antifungal activities and also anticancer properties resulting from the specific increase of the free radicals and oxidative stress caused in cancer cells. The antiproliferative effect was assessed by colorimetric assay of [3- (4,5- dimethylthiazol-2-l) -2,5-diphenyl tetrazolium MTT reagent in HeLa and NHDF cell lines. The permeability of the compounds was evaluated in the Ussing chamber using vaginal tissue and quantified by the high-performance liquid chromatography (HPLC) method. The formulations were also characterized in terms of pH buffering capacity, osmolality, viscosity and bioadhesion. The TEO formulations loaded with MTX and C8 showed an increase of antiproliferative effect, indicating that TEO may be an enhancer of the cytotoxic effect of MTX and C8 in cervical cancer cell lines. However, TEO showed some toxicity in both HeLa cells and normal cells (NHDF), presenting a greater antiproliferative effect in HeLa cells, in most formulations at concentrations of 1% and 0.4%. The formulations did not present the ideal technological properties (pH, buffering capacity, osmolality, viscosity and bioadhesion); however, in dilutions of vaginal fluid simulant presented the expected results. Overall, the formulations containing thyme and T1% + C8 developed under this project are the most promising in terms of cost-benefit and topical application for the treatment of lesions caused by HPV.
Description
Keywords
Derivado de Laranja de Acridina Formulações Vaginais Mitoxantrona Óleo Essencial de Thymus Vulgaris Simulante de Fluído Vaginal