Geles termorreversíveis na veiculação de fármacos

Orientação: Maria Lídia PalmaGeles termorreversíveis constituem um potencial sistema para a libertação controlada de fármacos. Estes geles gelificam a determinada temperatura, isto é, quando se encontram a baixas temperaturas comportam-se como soluções e a temperaturas específicas comportam-se como geles, aumentando o tempo de residência do fármaco no alvo. Apresentam-se, portanto, como uma aposta promissora para várias vias de administração de fármacos tais como oftálmica, rectal e aplicação tópica. O objetivo deste trabalho de campo foi o desenvolvimento e caracterização de quatro hidrogeles termorreversíves usando diferentes composições de polímeros: Poloxamer® F127; F127 com quitosano; F127 com carbómero® 940; F127 com goma xantana. Os geles foram preparados com base no método “Cold” com algumas adaptações. Os geles depois foram caracterizados em termos de viscosidade, análise térmica e da citotoxicidade geral tendo como referência base o modelo de Sacchamoryces Cerevisiae. Neste estudo observou-se um aumento de viscosidade proporcional ao aumento da temperatura. Todos os geles se comportaram como soluções a 4°C e como geles a 37°C. Os resultados da análise térmica evidenciaram a transição de estado através dos termogramas obtidos. As imagens obtidas com recurso ao SEM demonstraram a presença de cavidades/poros. Quanto ao estudo da citotoxicidade, este estudo sugere os geles não apresentam citotoxicidade no modelo utilizado. Concluindo, este trabalho de campo reforça a possível aplicação de geles termoreversíveis como veículo de libertação controlada de fármacos. No futuro irão ser realizados novos passos, incluindo a preparação de nanopartículas e sistemas lipídicos e a sua incorporação nos diferentes geles termorreversíves. Para corroborar estes resultados deverão ainda ser realizados estudos de permeação e adesão in vitro e in vivo bem como de citotoxicidade usando um modelo que inclua outros modelos celulares mais complexos.Thermo-reversible gels are a potential system for controlled drug delivery. These gels gel at a certain temperature, i.e. when at low temperatures behave as solutions and at specific temperatures behave as gels, increasing the residence time of the drug in the target. They are, therefore, presented as a promising bet for various routes of administration of drugs such as parenteral, ophthalmic, rectal and topical application. The aim of this study, was the development and characterization of four thermoreversible hydrogels using different polymer compositions: Poloxamer® F127; F127 with chitosan; F127 with carbomer® 940; F127 with xanthan gum. The gels were prepared based on the Cold method with some adaptations. The gels were then characterized in terms of viscosity, thermal analysis and general cytotoxicity with reference to the Saccharomyces cerevisiae model. In this study it was observed that a proportional increase in viscosity was observed with the increase in temperature. All gels behaved as solutions at 4 ° C and as gels at 37 ° C. The results of the thermal analysis showed the state transition through the obtained thermograms. The images obtained using SEM showed the presence of cavities / pores. Regarding the study of cytotoxicity, this study suggests gels do not present cytotoxicity in the model used. In conclusion, this experimental study reinforces the application of thermoreversible gels as a vehicle for controlled release of drugs, improving their efficacy. Further steps will be taken in the future, including the preparation of nanoparticles and lipid systems and their incorporation into the different thermoreversive gels. In order to corroborate these results, in vitro and in vivo permeation and adhesion studies as well as cytotoxicity should be performed using a model that includes other more complex cellular models

The Genome of Anopheles darlingi, the main neotropical malaria vector

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vectorhuman and vectorparasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible at www.labinfo.lncc.br/index.php/anopheles- darlingi. © 2013 The Author(s)