Encapsulamento de fármacos em zeólitos para utilização no tratamento do carcinoma do colorretal

Dissertação de mestrado em Técnicas de Caracterização e Análise QuímicaDesde a antiguidade que o Homem tem desenvolvido estratégias terapêuticas que têm sido aperfeiçoadas ao longo do tempo. A maioria das formulações terapêuticas apresenta uma ação rápida, de curta duração, atingindo um pico seguindo-se a diminuição rápida da sua ação. Tal levou à necessidade de se criarem formulações que permitam uma ação mais prolongada no tempo. Algumas destas novas formulações incluem os chamados sistemas drug delivery (DDSs), que podem ser direcionados para locais específicos do corpo. Estes sistemas, devido à sua capacidade de libertar os fármacos em locais específicos do corpo, apresentam inúmeras vantagens, como por exemplo, diminuição da toxicidade e maior tempo de permanência em circulação. São diversos os materiais que, durante as últimas décadas, têm sido estudados para a criação de DDSs. Estes sistemas têm sido sujeitos a diferentes abordagens de forma a aumentar o benefício terapêutico do fármaco minimizando os seus efeitos colaterais e ainda de forma a melhor as suas propriedades farmacocinéticas e farmacodinâmicas. Neste trabalho foram preparados DDSs baseados em três zeólitos, NaY, NanoNa-Y e KLTL, através do método de adsorção do fármaco em fase líquida. O fármaco utilizado para o encapsulamento foi o 5-fluoro-1H,3H-pirimidina-2,4-diona, que é um fármaco muito utilizado no tratamento de cancros sólidos, como o cancro colorretal. Os sistemas obtidos foram caraterizados para avaliar o efeito do encapsulamento do fármaco na estrutura dos zeólitos e para averiguar a presença do fármaco nos zeólitos. Os resultados obtidos mostram que o fármaco foi encapsulado com sucesso na estrutura zeolítica e que o mesmo não provoca alterações estruturais no zeólito. Posteriormente foram realizados estudos de libertação de fármaco a partir dos sistemas drug delivery preparados utilizando a técnica de cromatografia líquida de alta eficiência. Os sistemas foram sujeitos a duas condições experimentais, repouso e agitação. A agitação proporciona a libertação de maior quantidade de fármaco dos sistemas para a meio onde se encontram. Por fim, avaliou-se a eficácia dos sistemas drug delivery em duas linhas celulares do carcinoma colorretal, HCT-15 e RKO. O sistema que permitiu a obtenção de melhores resultados em ambas as linhas celulares foi o sistema preparado com o zeólito NaY. Verificou-se também que estes sistemas, para além de permitirem uma diminuição da viabilidade celular, permitem ainda uma potenciação do efeito do fármaco. Através de microscopia ótica e de microscopia de fluorescência, verificou-se que os zeólitos conseguem internalizar-se nas células.Since ancient times, man has developed therapeutic strategies that have been improved over time. Most therapeutic formulations have quick action, with short duration, reaching a peak followed by rapid decrease in its action. This led to the need to create formulations that allow a more prolonged action in time. Some of these new formulations include the so-called drug delivery systems (DDSs), which maybe targeted to a specific site in the body. These systems, due to their ability to release drugs at specific locations of the body have numerous advantages, for example, reduced toxicity and increased time in circulation. In last decades, several materials have been studied for the creation of DDSs. These systems have been subject to different approaches to increase the therapeutic benefit of the drug while minimizing the side effects and even to improve their pharmokinetic and pharmodynamic properties. In this work DDSs were prepared based on three zeolites, NaY, NanoNa-Y and KLTL, by the method of adsorption of the drug in liquid phase. The drug used for the encapsulation was the 5- Fluoro-2,4(1H,3H)-pyrimidinedione, that is a drug widely used in the treatment of solid tumors, such as colorectal cancer. The systems were characterized to evaluate the effect of encapsulation of the drug in the zeolite structure and to determine the presence of the drug in the zeolites. The results show that the drug was successfully encapsulated in the zeolite structure and it did not cause structural changes in the zeolite. After that, drug release studies were performed with the DDSs prepared using the technique of high performance liquid chromatography. Systems were subjected to two experimental conditions, rest and stirring. Stirring provided release of larger amounts of drug from the systems to the environment where they were. Finally, the efficacy of the DDSs was evaluated in two colorectal carcinoma cell lines, HCT-15 and RKO. The drug delivery system that allowed to obtain the best results in both cell lines was the system prepared with zeolite NaY. It was also found that these systems in addition to reducing cell viability, still allowed important potentiation of the drug. By light microscopy and fluorescence microscopy, there was evidence that zeolites were internalized by the cells

A cultura participativa digital entre consumidor e marca na experiência Farm

O cenário midiático contemporâneo instiga questionamentos quanto às dinâmicas realizadas em redes de sociabilidade. Tais dinâmicas tornaram-se oportunas para a construção de diálogos entre organizações e consumidores. Nesse sentido, as redes de sociabilidade estabeleceram um vínculo de proximidade com seus respectivos consumidores tornando-se possíveis canais de atendimento ao consumidor, onde perpassam aspectos positivos e negativos referentes aos produtos comercializados. Nesse contexto, o presente estudo propõe, em um primeiro momento elucidar possíveis diálogos existentes na relação entre marca e consumidores existentes na cultura participativa, além de compreender melhor como tais canais se transformaram em verdadeiros canais de atendimento aos consumidores. Uma evidência deste processo é a marca carioca Farm. Para atendimento da meta de conhecimento, os seguintes procedimentos metodológicos estabelecidos incluem: revisão bibliográfica de autores pertinentes ao tema, além de uma pesquisa de observação, baseada em uma inspiração etnográfica na principal rede social da marca: o Instagram

Zeolite structures as cancer-targeted drug delivery carriers

Tese de Doutoramento em Ciências (Especialidade em Química)Cancer is one of the major health problems worldwide, counting thousands of new cases and deaths annually. The current modalities for cancer treatment include surgery, chemotherapy, radiotherapy and immunotherapy. However, occasionally some of these modalities cannot be used due to the stage of the tumor or have insufficient effect in tumor regression, whereby new therapy strategies are needed. The application of nanotechnology in cancer treatment opened the opportunity to develop new strategies, and drug delivery systems (DDS) can be found among them. The use of DDS has been reported in several studies as a promising approach for delivering drugs to the place of action and reduce the drawbacks of conventional drug administration. To develop these systems, biocompatible and non-toxic materials are needed, where the selected drug can be loaded. Among the several materials that could be used for DDS preparation, are zeolites. The main objective of this work was the development of effective DDS based on zeolites to be used in breast and colorectal cancer treatment. Thus, several structures and their potential as carriers were investigated, as well as the mechanisms underlying zeolite internalization, exploring surface functionalization on zeolite toxicity and uptake by human cells and exploring the use of zeolites as magnetic resonance imaging agents. The potential of the use of the anti-inflammatory drug salicylic acid, for breast cancer treatment, loaded into silica microporous and mesoporous structures, was assessed. It was observed that mesoporous structures had higher drug loading capacity than microporous structures. In terms of cytotoxicity, only DDS prepared with mesoporous structures were able to decrease cell growth. Overall, the results indicated the potential of salicylic acid for cancer treatment when loaded into mesoporous structures, but not when loaded into microporous structures. So, in order to study the potential of the microporous structures as host for DDS, an anticancer drug was used. Then, three different zeolites (NaY, NaA and ZSM5) and one titanosilicate (ETS-10) were investigated as carriers for the anticancer drug 5-fluorouracil (5-FU) in order to select the most promising zeolite structures for further studies. The results showed the biocompatibility of these microporous structures since they were not toxic to colon or breast cancer cells. In addition, loading 5-FU in these structures led to potentiation of 5-FU and allowed the selection of two zeolites, NaY and LTL for the next studies. To finalize the exploration of the potential of zeolite for DDS preparation, DDS were prepared, and their in vitro and in vivo efficacy were assessed. Results of the in vitro studies confirmed the potential of the DDS prepared with NaY and LTL (Zeo L) for breast, colorectal and melanoma cancers treatment since there was a significant inhibition of cell growth when cells are treated with the DDS, with potentiation of 5-FU effect compared to the free drug. However, in vivo studies using the chick embryo chorioallantoic membrane as model (CAM) revealed that DDS induced a reduction in tumor perimeter for breast cancer cells, while no reduction was detected for colon tumors, under the used concentration of DDS. Zeolite NaY magnetization revealed its potential as magnetic resonance imaging agent, opening new opportunities to prepare hybrid systems combining the encapsulating and delivery properties of the zeolites and the magnetic properties of biocompatible magnetite nanoparticles. Considering the scarce studies on the internalization mechanisms of zeolite nanoparticles, the endocytic mechanisms involved in their internalization by human cells were explored. The results showed that zeolite internalization is likely mediated by caveolin-dependent endocytosis and it is also dependent on microtubule polymerization pathways. In these studies, the uptake of zeolite nanoparticles was assessed in the same cell lines. It was found that cancer cells internalize higher amounts of zeolite nanoparticles and at a faster rate than normal cells. The effect of zeolite surface functionalization plays also an important role in the cellular uptake. Based on the observations from these studies, it was possible to observe that positively-charged zeolite nanoparticles present higher uptake rates than negatively-charged zeolite nanoparticles. This work provides a valuable contribution to the use of zeolites as carriers for DDS preparation and presents novel evidences about the biological mechanisms enrolled in the uptake of zeolite nanoparticles by human cells. Thus, the work performed in this thesis is not an end of a research project, but an important contribution to a better design of DDS based on zeolitic structures, opening new horizons for the application of these DDS in cancer treatment.O cancro constitui um dos maiores problemas de saúde no mundo, contando anualmente com milhares de novos casos e mortes. As atuais abordagens de tratamento do cancro incluem cirurgia, quimioterapia, radioterapia e imunoterapia. Contudo, por vezes algumas não podem ser utilizadas devido à fase avançada do tumor ou por apresentarem pouco efeito na regressão do mesmo, pelo que são necessárias novas abordagens terapêuticas. A aplicação da nanotecnologia no tratamento do cancro, abriu a oportunidade de desenvolver novas estratégias, contando-se entre estas os sistemas de libertação de fármacos. Vários estudos têm reportado o uso destes sistemas como uma abordagem promissora para a entrega de fármacos no local de ação e na redução dos efeitos secundários associados aos sistemas de administração convencionais. Para o desenvolvimento de sistemas de libertação de fármacos, são necessários materiais biocompatíveis e não tóxicos onde o fármaco possa ser inserido. Entre o grande número de materiais que podem ser usados para a preparação destes sistemas, encontram-se os zeólitos. O principal objetivo deste trabalho foi desenvolver sistemas de libertação de fármacos baseados em zeólitos para o tratamento do cancro colorretal e da mama. Assim, foram exploradas várias estruturas e avaliado o seu potencial como transportadores de fármacos, bem como os mecanismos subjacentes à internalização das partículas de zeólitos por células humanas tumorais. Foi também avaliado o efeito da funcionalização da superfície na toxicidade e internalização das nanopartículas nas células e explorado o uso de zeólitos como agentes para imagem de ressonância magnética (MRI). Foi avaliado o potencial do uso do anti-inflamatório ácido salicílico para o tratamento do cancro da mama quando encapsulado em estruturas de sílica micro- e mesoporosas. Observou-se que as estruturas mesoporosas apresentavam maior capacidade de encapsulamento do fármaco do que as estruturas microporosas. Em termos de citotoxicidade, apenas os sistemas de libertação de fármacos preparados com estruturas mesoporosas foram capazes de reduzir o crescimento celular. No geral, os resultados indicaram o potencial do ácido salicílico para o tratamento do cancro quando encapsulado em estruturas mesoporosas, mas não quando encapsulado em estruturas microporosas. Assim, para estudar o potencial do uso das estruturas microporosas como material para a preparação de sistemas de libertação, foi utilizado um fármaco antineoplásico. Neste contexto, três zeólitos diferentes (NaY, NaA e ZSM5) e um titanosilicato (ETS-10) foram explorados como suportes para o fármaco antineoplásico 5-fluorouracilo (5-FU), de forma a selecionar as estruturas mais promissoras para os estudos seguintes. Os resultados demonstraram que estes materiais são biocompatíveis, uma vez que não se revelaram tóxicos para células do cancro colorretal e mama. Além disso, o encapsulamento do 5-FU nestas estruturas, levou a uma potenciação do seu efeito. Este estudo permitiu a seleção de duas estruturas zeolíticas, NaY e LTL, para os estudos subsequentes. Para finalizar a exploração do potencial dos zeólitos para a preparação de sistemas de libertação de fármacos, foram preparados sistemas usando os zeólitos NaY e L, e a sua eficácia in vitro e in vivo foi avaliada. Os resultados dos estudos in vitro confirmaram o potencial dos sistemas de libertação preparados com os zeólitos NaY e LTL (Zeo L) no tratamento do cancro da mama, colorretal e melanoma, uma vez que se verificou uma inibição significativa do crescimento celular quando as células foram tratadas com os sistemas. Verificou-se ainda uma potenciação do 5-FU quando comparado com o fármaco livre. Contudo, os estudos in vivo usando o modelo membrana corioalantóide de embrião de galinha (CAM), mostraram que, na concentração usada, os DDS induziram a redução dos tumores da linha Hs 578T, mas não dos tumores da linha RKO. A magnetização do zeólito NaY revelou o seu potencial como agente para MRI, abrindo novas oportunidades para a preparação de sistemas híbridos que combinem as propriedades de encapsulação e libertação dos zeólitos e, as propriedades das nanopartículas magnéticas. Uma vez que há poucos estudos sobre os mecanismos de internalização das nanopartículas de zeólitos, foram também estudados os mecanismos envolvidos na sua internalização em células humanas. Os resultados mostraram que a internalização dos zeólitos é principalmente mediada pela endocitose dependente da caveolina, sendo também dependente das vias envolvidas na polimerização dos microtúbulos. Nestes estudos, verificou-se ainda a internalização dos zeólitos em células humanas e observou-se que as células cancerígenas internalizam maior quantidade de zeólito a uma taxa mais rápida do que as células normais. Concluiu-se também que o efeito da funcionalização da superfície dos zeólitos desempenha um papel importante na internalização celular. Os resultados obtidos mostraram que nanopartículas de zeólitos positivamente carregadas têm maior capacidade de internalização do que partículas negativamente carregadas. Em suma, este trabalho fornece uma contribuição importante sobre o uso de zeólitos para a preparação de sistemas de libertação controlada de fármacos e apresenta novas evidências sobre os mecanismos biológicos envolvidos na internalização dos zeólitos em células humanas. Assim, o trabalho desenvolvido nesta tese poderá contribuir para o desenvolvimento de melhores sistemas de libertação de fármacos baseados em estruturas zeolíticas, abrindo novos horizontes para a sua aplicação no tratamento do cancro.The research work here presented was financially supported by an individual fellowship (SFRH/BD/97797/2013) and by the strategic fundings of Centre of Chemistry (UID/QUI/00686/2013 and UID/QUI/0686/2016) and ICVS/3B’s (POCI-01-0145-FEDER-007038) from the Fundação para Ciência e Tecnologia (FCT) and European Regional Development Fund (FEDER) funds, through the Competitiveness Factors Operational Programme (COMPETE). The projects: NORTE-01-0145-FEDER-000013 and BioTecNorte (operation NORTE-01-0145-FEDER-000004), from Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, were also sponsoring this work. Part of this work was also partially supported by the NORTE 2020 and the FEDER under the Grant NORTE-45-2015-02, and by European Union's Horizon 2020 research and innovation programme under grant agreement Nº 686009

Evaluation of the potential of agro-industrial waste-based composts to control Botrytis gray mold and soilborne fungal diseases in lettuce

Composts are widely used in horticulture as organic amendments to improve the properties of soils. Composts have also been reported to enhance the disease suppressive potential of soils and, therefore, could be used as a strategy for managing plant diseases. The aim of this study was to test the ability of soils amended with four different agro-industrial waste-based composts (chestnut peels and shells, spent coffee grounds, grape marc, and olive leaves) to inhibit the growth and activity of Botrytis cinerea and several soilborne pathogens. First, the capacity of aqueous compost extracts to inhibit the growth of Botrytis cinerea and five soilborne fungi was evaluated in vitro using a broth macrodilution method. Second, lettuce plants were grown on soils amended with composts and inoculated either with B. cinerea or the soilborne fungus Fusarium oxysporum Schlechtendahl isolated from lamb’s lettuce. The determination of minimal inhibitory concentrations indicated that none of the composts inhibited the mycelium growth of the selected fungal pathogens. However, the pathogens did not cause any damage on plants grown on the chestnut- and olive-based composts. Lettuce yields were also highest for plants grown with composts made from chestnut and olive, irrespective of the amount of compost incorporated into soils (5% or 10%, weight basis). The grape-based compost also exhibited a fertilization effect, although the effect was associated with increased Fusarium wilt severity. Both N immobilization and symbiosis with the compost’s microflora were used to explain the pathogenicity of F. oxysporum Schlechtendahl in response to amendment with composts made from grape and coffee wastes. The beneficial effects of the chestnut- and olive-based composts reported in this study could be exploited in strategies aimed at reducing reliance on synthetic pesticides for the control of fungi in lettuce cultivation.This work was supported by European Investment Funds (FEDER/COMPETE/POCIOperational Competitiveness and Internationalization Program) under the project POCI-0145-FEDER006958 and by national funds provided by FCT—Portuguese Foundation for Science and Technology, under the projects PTDC/AGR-AAM/102006/2008, SFRH/BD/81473/2011 and UIDB/04033/2020

Optimization of iron-ZIF-8 catalysts for degradation of tartrazine in water by Fenton-like reaction

Optimization of iron zeolitic imidazole framework-8 (FeZIF-8) nanoparticles, as heterogeneous catalysts, were synthesized and evaluated by the Fenton-like reaction for to degrade tartrazine (Tar) in aqueous environment. To achieve this, ZIF-8 nanoparticles were modified with different iron species (Fe2+ or Fe3O4), and subsequently assessed through the Fenton-like oxidation. The effect of different parameters such as the concentration of hydrogen peroxide, the mass of catalyst and the contact time of reaction on the degradation of Tar by Fenton-like oxidation was studied by using the Box-Behnken design (BBD). The BBD model indicated that the optimum catalytic conditions for Fenton-like reaction with an initial pollutant concentration of 30ppm at pH 3.0 were T=40°C and 12mM of H2O2, 2g/L of catalyst and 4h of reaction. The maximum Tar conversion value achieved with the best catalyst, Fe1ZIF-8, was 66.5% with high mineralization (in terms of decrease of total organic carbon TOC), 44.2%. To assess phytotoxicity, the germination success of corn kernels was used as an indicator in the laboratory. The results show that the catalytic oxidation by Fenton-like reaction using heterogeneous iron ZIF-8 catalysts is a viable alternative for treating contaminated effluents with organic pollutants and highlighted the importance of the validation of the optimized experimental conditions by mathematical models.O.A. thanks to ERASMUS + Program for the mobility Ph.D. grant and A.R.B. thanks to Fundação para Ciência e Tecnologia, FCT (Portugal) for her Ph.D. grant (SFRH/BD/141058/2018). This research work has been funded by national funds funded through FCT/MCTES (PIDDAC) over the projects: LA/P/0045/2020 (ALiCE), UIDB/50020/2020 and UIDP/50020/2020 (LSRE-LCM), Centre of Chemistry (UID/QUI/0686/2020), CEB (UIDB/04469/2020) and project BioTecNorte (operation NORTE-01-0145-FEDER-000004), supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).info:eu-repo/semantics/publishedVersio

Potentiation of 5-fluorouracil encapsulated in zeolites as drug delivery systems for in vitro models of colorectal carcinoma

The studies of potentiation of 5-fluorouracil (5-FU), a traditional drug used in the treatment of several cancers, including colorectal (CRC), were carried out with zeolites Faujasite in the sodium form, with different particle sizes (NaY, 700nm and nanoNaY, 150nm) and Linde type L in the potassium form (LTL) with a particle size of 80nm. 5-FU was loaded into zeolites by liquid-phase adsorption. Characterization by spectroscopic techniques (FTIR, 1H NMR and 13C and 27Al solid-state MAS NMR), chemical analysis, thermal analysis (TGA), nitrogen adsorption isotherms and scanning electron microscopy (SEM), demonstrated the successful loading of 5-FU into the zeolite hosts. In vitro drug release studies (PBS buffer pH 7.4, 37°C) revealed the release of 80-90% of 5-FU in the first 10min. To ascertain the drug release kinetics, the release profiles were fitted to zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas and Weibull kinetic models. The in vitro dissolution from the drug delivery systems (DDS) was explained by the Weibull model. The DDS efficacy was evaluated using two human colorectal carcinoma cell lines, HCT-15 and RKO. Unloaded zeolites presented no toxicity to both cancer cells, while all DDS allowed an important potentiation of the 5-FU effect on the cell viability. Immunofluorescence studies provided evidence for zeolite-cell internalization.RA is recipient of fellowship SFRH/BI/51118/2010 from Fundacao para a Ciencia e a Tecnologia (FCT, Portugal). This work was supported by the FCT projects refs. PEst-C/QUI/UI0686/2011 and PEst-C/CTM/LA0011/2011 and the Centre of Chemistry and Life and Health Sciences Research Institute (University of Minho, Portugal). The NMR spectrometer is part of the National NMR Network (RNRMN), supported with funds from FCT/QREN (Quadro de Referencia Estrategico Nacional)

Dermatite atópica pediátrica: fisiopatologia e manejo terapêutico / Pediatric atopic dermatitis: pathophysiology and therapeutic management

A dermatite atópica (DA), conhecida também como eczema atópico, é uma condição inflamatória crônica recidivante que acomete o tecido cutâneo. No que tange às estatísticas gerais, a incidência de DA aumentou de 2 a 3 vezes nos países industrializados, afetando aproximadamente 15% a 20% das crianças e 1% a 3% dos adultos em todo o mundo. A DA, em termos fisiopatológicos, é uma afecção inflamatória crônica recidivante da pele, multifacetada, comumente associada a outras manifestações atópicas, como alergia alimentar, rinite alérgica e asma. O início da doença é mais comum aos 5 anos de idade, sendo o diagnóstico e o tratamento precoces essenciais para evitar complicações da DA e melhorar a qualidade de vida. Há muitas condições de pele que podem mimetizar essa doença, sendo possível até mesmo coexistirem e/ou agravarem a DA, que devem ser excluídas ao diagnosticá-la, tais como: dermatite seborreica, sarna, dermatite de contato, psoríase, linfoma cutâneo de células T, dentre outras afecções cutâneas. O tratamento da DA objetiva condutas multifatoriais, das quais dependem da associação de medidas não farmacológicas e farmacológicas, sendo prescrita de acordo com o grau da doença. É imprescindível que os portadores de DA sejam esclarecidos e aderentes às medidas não farmacológicas para prevenção de crises agudas. Nesse sentido, cita-se a necessidade do uso de hidratantes neutros em toda a pele após banhos diários, evitando cremes e sabonetes com produtos alérgenos, além de não se submeterem a extremos de calor, frio ou umidade. Associado a essas medidas, o tratamento farmacológico tem se mostrado muito eficaz em casos mais graves e recidivantes

Zeolite structures loading with an anticancer compound as drug delivery systems

The authors are thankful to Dr. A. S. Azevedo for collecting the powder diffraction data.Two different structures of zeolites, faujasite (FAU) and Linde type A (LTA), were studied to investigate their suitability for drug delivery systems (DDS). The zeolites in the sodium form (NaY and NaA) were used as hosts for encapsulation of α-cyano-4- hydroxycinnamic acid (CHC). CHC, an experimental anticancer drug, was encapsulated in both zeolites by diffusion in liquid phase. These new drug delivery systems, CHC@zeolite, were characterized by spectroscopic techniques (FTIR, 1H NMR, 13C and 27Al solidstate MAS NMR, and UV−vis), chemical analysis, powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). The effect of the zeolites and CHC@zeolite drug deliveries on HCT-15 human colon carcinoma cell line viability was evaluated. Both zeolites alone revealed no toxicity to HCT-15 cancer cells. Importantly, CHC@zeolite exhibit an inhibition of cell viability up to 585-fold, when compared to the non-encapsulated drug. These results indicate the potential of the zeolites for drug loading and delivery into cancer cells to induce cell deathO.M. and R.A. are recipients of fellowships (SFRH/BD/36463/2007, SFRH/BI/51118/2010) from Fundação para a Ciência e a Tecnologia (FCT, Portugal). This work was supported by the FCT projects refs PEst-C/ QUI/UI0686/2011, PEst-C/CTM/LA0011/2011, and PTDC/ SAU-FCF/104347/2008, under the scope of “Programa Operacional Temático Factores de Competitividade” (COMPETE) of “Quadro Comunitário de Apoio III” and cofinanced by Fundo Comunitário Europeu FEDER, and the Centre of Chemistry and Life and Health Sciences Research Institute (University of Minho, Portugal)

Zeolites: promising candidates for drug delivery systems (DDSs)

[Excerpt] The aim of controlled drug delivery systems (DDSs) is to administer the necessary amount of drug safely and effectively to specific sites in the human body and to regulate the temporal drug profile for maximum therapeutic benefits.[1] Zeolites are crystalline aluminosilicates solids with very regular microporous structures and they have been recently considered for medical use due to their biological properties and stability in biological environments.[1,2] The large variety in pore structures and morphologies provided by different types of molecular sieves offers unique possibilities for the design of host-guest systems with particular properties.[3] One of the many potentially medicinal applications of zeolites is the encapsulation of different drug molecules into them so as to obtain subsequent DDSs. 5-fluoro-1H-pyrimidine-2,4-dione (5-FU), a drug traditionally used in anticancer treatment of colorectal carcinoma (CRC)[4] was chosen as a guest in zeolite structure for DDS. The zeolite in sodium form (NaY) was used for encapsulation of 5-FU as a guest, by diffusion in liquid phase in the void space of the host zeolite. The new DDS, 5-FU@zeolite, was evaluated by several techniques (FTIR, UV-vis, XRD, SEM and chemical analysis). The cytotoxic effect of the zeolite and 5-FU@zeolite on RKO and HCT-15 human colon carcinoma cell line viability was evaluated. The results show that 5-FU@zeolite has a significantly higher inhibitory effect on the viability of both cell lines (assessed by Sulforhodamine B assay), as compared to 5-FU alone. [...]Acknowledgements: This work was supported by the Centre of Chemistry and Life and Health Sciences Research Institute (University of Minho, Portugal), FCT (Portugal) through POCTI and FEDER projects (F-COMP-01-0124-FEDER-022716, refª FCT PEst-C/QUI/UI0686/2011), POCTI-SFA-3-686) and by the FCT grant ref. PTDC/SAU-FCF/104347/2008, under the scope of “Programa Operacional Temático Factores de Competitividade” (COMPETE) of “Quadro Comunitário de Apoio III” and co-financed by Fundo Comunitário Europeu FEDER