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A espécie vegetal Parkinsonia aculeata, pertencente à subfamília Caesalpiniaceae da família Fabaceae, é uma árvore de uma espécie de porte arbustivo-arbóreo oriunda de regiões semiáridas da América tropical, caracteriza-se como uma pequena árvore caducifólia espinhosa que apresenta casca verde ou marrom; folhas bipinadas; flores perfumadas tipo racemos e de coloração amarela; fruto do tipo vagem, no Brasil pode ser encontrada no Nordeste. É um exemplo de planta medicinal utilizada pela população e curandeiros e, dentre os seus principais constituintes químicos, destacam-se os taninos glicosados, flavonóides e esteróides que possuem uma potente ação no tratamento de resistência insulínica. Dentre as propriedades observadas nas diversas partes da planta, foi constatado que as partes aéreas da P. aculeata possuem substâncias que apresentam atividade anti-hiperglicemiante. Desta forma, este trabalho visa caracterizar físico-quimicamente a droga vegetal e solução extrativa obtidos a partir das partes aéreas de Parkinsonia aculeata para desenvolvimento de forma farmacêutica como futura alternativa no tratamento de resistência insulínica. O material vegetal de P. aculeata foi coletado na região do Xingó-SE. Suas partes aéreas foram secas e trituradas. A solução extrativa foi obtida através da maceração da matéria-prima e as caracterizações foram realizadas de acordo com a Farmacopeia Brasileira.

Background: Albendazole (ABZ) is the drug of choice for the treatment of a variety of human and veterinary parasites. However, it has low aqueous solubility and low bioavailability. Cyclodextrins (CD) are pharmaceutical excipients with the ability to modulate the solubilization property of hydrophobic molecules. Objective: The aim of the study was to analyze through in vitro and in silico studies (Autodock Vina software and CycloMolder platform) the formation of inclusion complexes between ABZ, β-cyclodextrin (β-CD) and its derivatives Methyl-β-cyclodextrin (M-β-CD) and Hydroxypropyl-β-cyclodextrin (HP-β-CD). Methods: The most stable inclusion complexes were produced by the kneading method and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), determination of the ABZ content and in vitro dissolution profile. Results: Molecular modeling revealed that inclusion complexes between HP-β-CD:ABZ (in the proportion 1:1 and 2:1) presented the lowest formation energy and the highest number of intermolecular interactions, showing that the use of more cyclodextrins does not generate gains in the stability of the complex. On the characterization tests, the complexes experimentally obtained by the kneading method demonstrated highly suggestive parameters, including ABZ in HP-β-CD in both molar proportions, suppression of bands in the infrared spectrum, displacement of the drug's melting temperature in DSC, crystallinity halos instead of the characteristic peaks of ABZ crystals in the XRD and a release of more than 80% of ABZ in less than 5 minutes, dissolution efficiency of up to 92%. Conclusion: In silico studies provided a rational selection of the appropriate complexes of cyclodextrin, enabling the elaboration of more targeted complexes, decreasing time and costs for elaboration of new formulations, thereby increasing the oral biodisponibility of ABZ.

In this work, we investigated in vitro the antioxidant, cytotoxic and anti-leishmanial activities of a lignin extracted from the leaves of Morinda citrifolia. Initially, an analysis of the composition of the sheets was performed, then the lignin was obtained by alkaline delignification and characterized by different techniques: elemental analysis, FT-R, UV–vis, HSQC-NMR, thermal analysis, Py-GC/MS and by GPC. The results showed that the leaves had in their composition cellulose (31.29%), hemicellulose (25.01%), lignin (18.34%), extractives (14.39%) and ash (10.03%). The lignin extraction yield was 89.8%. The lignin obtained is of the GSH type with the following contents 79.39%, 13.58% and 7.03% respectively. Furthermore, it is low molecular weight and thermally stable. It had a phenolic content of 93.3 mg GAE/g and low antioxidant activity. In macrophage cytotoxicity assays, it presented a CC50 of 31.0 μg/mL, showing less toxicity than amphotericin B. In assays against the promastigote forms of Leishmania amazonensis, lignin presented an IC50 of 29.56 μg/mL, a less effective concentration than amphotericin B (IC50 = 0.14 μg/mL). However, it was able to promote inhibition of the parasites, a fact confirmed by structural changes. These findings reinforce that M. citrifolia lignin is a promising macromolecule for use as an antiparasitic and antioxidant agent.

Introduction: Metal organic frameworks (MOFs) are a recent group of nano porous materials with exceptional physical properties, such as large surface areas, high pore volumes, low densities and wel...

The present work aimed at developing pharmaceutical dosage forms based on the dry bark extract of Libidibia ferrea for the treatment of diabetes mellitus . The physicochemical characterization of the plant raw material, extractive solution and dry extract obtained by freeze drying were carried out. Effervescent granules, oral solution and tablets from the dry extract were developed and subjected to the recommended quality control tests. All materials presented standardized values after physical-chemical characterization. The presence of several secondary compounds was confirmed, and the content of the tannins was determined. The extract did not present acute toxicity in the in vivo experiment and provided an increase in glucose uptake in the in vitro study. The developed formulations complied with previously established values for quality control. The results show the safety and efficacy of the developed products, may being promising options in the treatment of diabetes mellitus .

Background: Inflammation is an essential response provided by the immune system, ensuring the survival during microbial infection, tissue injury and other noxious conditions. However, prolonged inflammatory processes are often associated with severe side effects on health. Objective: This systematic review aimed to provide the evidence in the literature of the preclinical and human anti-inflammatory activity of gallium compounds from 2000 to 2019 focused on elucidating the mechanisms involved in the inflammatory process. Methods: Seven bibliographical databases were consulted (PubMed, Medline, ScienceDirect, Scopus, Springer, Web of Science, and EBSCOhost). The selection of appropriate publications and writing of this systematic review were based on the guidelines mentioned in the PRISMA statement. Moreover, the assessment of the methodological quality of the selected studies was also performed. Results: From a total of 3018 studies, 16 studies were included in this paper based on our eligibility criteria, which showed promising and consistent results. Conclusion: Further research concerning specific inflammatory conditions is required.

Funding Information: The authors acknowledge Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco ( FACEPE ) for a scholarship. This study was supported by funding from the Spanish Group CTS-946 and project P18-RT-3786 . Publisher Copyright: © 2023 Elsevier B.V. Nanotechnology is a crucial technology in recent years has resulted in new and creative applications of nanomedicine. Polymeric nanoparticles have increasing demands in pharmaceutical applications and require high reproducibility, homogeneity, and control over their properties. Work explores the use of cashew phthalate gum (PCG) as a particle-forming polymer. PCG exhibited a pH-sensitive behavior due to the of acid groups on its chains, and control drug release. We report the development of nanoparticles carrying benznidazole. Formulations were characterized by DLS, encapsulation efficiency, drug loading, FTIR, pH-responsive behavior, release, and in vitro kinetics. Interaction between polymer and drug was an evaluated by molecular dynamics. Morphology was observed by SEM, and in vitro cytotoxicity by MTT assay. Trypanocidal effect for epimastigote and trypomastigote forms was also evaluated. NPs responded to the slightly basic pH, triggering the release of BNZ. In acidic medium, they presented small size, spherical shape, and good stability. It was indicated NP with enhanced biological activity, reduced cytotoxicity, high anti T. cruzi performance, and pH-sensitive release. This work investigated properties related to the development and enhancement of nanoparticles. PCG has specific physicochemical properties that make it a promising alternative to drug delivery, however, there are still challenges to be overcome. publishersversion published

The acquired immunodeficiency syndrome remains a major problem in worldwide public health and its antiretroviral treatment therapy combines at least three high activity classes of drugs. Access to antiretroviral treatment for HIV-infected patients is a global public health priority and efavirenz (EFZ) is one of the first drug choices. However, EFZ is classified as a class II drug, according to the biopharmaceutics classification system due to low solubility and high permeability, which leads it to fail in absorption and hence bioavailability. One of the approaches used to overcome these issues is the preparation of solid dispersions. In this study, thermal analysis and pyrolysis coupled with gas chromatography-mass spectrometry (GC/MS) were employed to determine efavirenz thermal stability and the solid dispersion with poly (vinylpyrrolidone-co-vinylacetate) (PVPVA 64). Thus, it suggests that EFZ was converted to its amorphous state, and there was an increase in EFZ thermal stability when it is dispersed in a polymer matrix compared to the drug alone, since there was an increase in the activation Energy (Ea) and a decrease in frequency factor (A). Furthermore, there was a change in the zero reaction order to one. The thermal stability time of the formulation was estimated at 7 months. In addition, it was possible to observe a good correlation between loss of mass and the technique of Pyrolysis-GC–MS and to posit the formation of new fragments, which clarifies the technique with regard to the identification of thermal decomposition fragments.

Background: Efavirenz is the most used medication in the treatment of Acquired Immunodeficiency Syndrome (AIDS). The limited number of pediatric antiretroviral formulations approved by regulatory agencies is the most significant obstacle to adequate and efficient pharmacotherapy for this group of patients. The efavirenz has excellent therapeutic potential, but has low aqueous solubility/bioavailability. Methods: To minimize these limitations, multicomponent systems with β-cyclodextrin and polyvinylpyrrolidone K-30 were obtained. Due to the limited number of pediatric antiretroviral formulations, the development of a pediatric orodispersible tablet is an alternative that is thought easy to administer, since it disintegrates rapidly in the oral cavity. The multicomponent systems were obtained by the method of kneading and characterized by solubility test, X-ray diffraction, differential scanning calorimetry and infrared absorption spectroscopy by Fourier transform. The orodispersible tablets were prepared by direct compression. The quality control of hardness, friability, disintegration, and dissolution was performed. The influence of the components of the formulation on the characteristics of the tablets was evaluated through a 22 factorial design added with three central points, to compare the effect of the dependent variables on the responses. Results: An increase in drug solubility was observed, with a decrease in crystallinity. Besides that, an excellent dissolution profile presented with more than 83% of the drug's content dissolved in less than 15 minutes. Satisfactory disintegration time and friability were observed. Conclusion: It was observed that reduced concentrations of mannitol decreased the hardness and disintegration time of the formulations. The orodispersible tablet composed of efavirenz: β- cyclodextrin: polyvinylpyrrolidone, favors greater absorption and bioavailability. It has several advantages for pediatric patients, as the dosage form disintegrates quickly in the mouth and does not require water for administration, thereby improving patient compliance with the treatment.

Chagas disease (CD), caused by the flagellate protozoan Trypanosoma cruzi, is one of the major public health problems in developing countries. Benznidazole (BNZ) is the only drug available for CD treatment in most countries, however, it presents high toxicity and low bioavailability. To address these problems this study used Zeolitic Imidazolate Framework-8 (ZIF-8), which has garnered considerable attention due to its potential applications, enabling the controlled delivery of drugs. The present work developed and characterized a BNZ@ZIF-8 system, and the modulation of BNZ release from the ZIF-8 framework was evaluated through the in vitro dialysis release method under sink conditions at different pH values. Moreover, the in vitro evaluation of cell viability and cytotoxicity by MTT assay were also performed. The dissolution studies corroborated that a pH sensitive Drug Delivery System capable of vectorizing the release of BNZ was developed, may leading to the improvement in the bioavailability of BNZ. The MTT assay showed that no statistically significant toxic effects occurred in the developed system, nor significant effects on cell viability.

Considered prevalent in many countries on five continents, especially in low-income regions, leishmaniasis is a neglected tropical disease classified by World Health Organization as one of the diseases for which the development of new treatments is a priority. It is an infectious disease caused by protozoa of the genus Leishmania, whose species may cause different clinical manifestations, such as cutaneous and visceral leishmaniasis (VL). Treatment is exclusively by drug therapy, as it has not been possible to develop vaccines yet. Currently available drugs are not fully effective in all cases; they have parenteral administration and exhibit a number of serious and very common adverse effects. The only oral drug available is expensive and it is not available in many endemic countries. Injectable administration is the main problem of treatments, since it requires patients to go to health centers, hospitalization and professional administration, which are conditions that are not adapted to the reality of the poverty conditions of patients with the disease. In this context, the development of an oral medicine has become a focus as it may solve many of these issues. Based on this scenario, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs directed to the treatment of human VL.

Diabetes mellitus (DM) pode ser definida como um grupo de disturbios metabolicos caracterizados por hiperglicemia resultante de defeitos na secrecao de insulina e/ou acao da insulina. O estado de hiperglicemia cronica nos pacientes com diabetes e extremamente preocupante e resulta em uma serie de complicacoes clinicas e gastos crescentes mundialmente relacionados ao seu tratamento. Libidibia ferrea e uma especie vegetal nativa do Brasil que vem sendo utilizada ha muitos anos na medicina popular e cujo potencial farmacologico esta sendo comprovado por inumeras pesquisas realizadas. Entre suas atividades farmacologicas, se destaca a sua atividade anti-hiperglicemiante. Sendo assim, o presente trabalho teve como objetivo desenvolver formas farmaceuticas solidas (capsulas) a base do extrato seco da casca do caule de Libidibia ferrea como alternativa para o tratamento de diabetes mellitus . Para isso, o material vegetal foi processado e caracterizado, como tambem sua solucao extrativa. Posteriormente, o extrato seco foi obtido por liofilizacao e submetido a testes de compatibilidade com excipientes. Por fim, foram manipuladas quatro formulacoes diferentes para obtencao das capsulas a partir do extrato seco que foram submetidas aos testes de controle de qualidade preconizados. Observou-se que a materia-prima vegetal, solucao extrativa e extrato seco apresentaram valores de caracterizacoes, conforme a Farmacopeia Brasileira 6a edicao e literaturas cientificas, no que diz respeito a determinacao granulometrica, de umidade, cinzas totais para a materia-prima vegetal; determinacao de densidade relativa, pH e residuo seco para o extrato aquoso e determinacao de umidade residual, prospeccao fitoquimica, doseamento de taninos, analise superficial e tamanho de poros para o extrato seco. Os testes de compatibilidade do extrato seco com os diferentes excipientes selecionados para as formulacoes foram satisfatorios, uma vez que nao foi observada nenhuma interacao que pudesse comprometer a escolha dos excipientes para as formulacoes determinadas. Quanto as capsulas obtidas, as mesmas apresentaram resultados dentro dos preconizados pela Farmacopeia Brasileira 6a edicao quanto ao peso medio e teste de desintegracao e tambem apresentaram teor de taninos de acordo com o esperado. As capsulas desenvolvidas de forma preliminar neste trabalho poderao viabilizar um novo tratamento fitoterapico para diabetes mellitus .

Triplaris gardneriana Wedd. (Polygonaceae) conhecida popularmente como “pajeu” e utilizada na medicina tradicional para tratar blenorragia, leucorreia, hemorroidas sangrentas, inflamacao dos orgaos internos, dor, entre outros. Dessa forma, e de suma importância o estudo para avaliar seus parâmetros de qualidade, uma vez que e bastante utilizada pela populacao. Com isso, objetivou-se realizar uma caracterizacao farmacognostica, termica e morfologica das cascas e folhas da especie. O material vegetal foi submetido aos ensaios de determinacao da granulometria dos pos, da perda por dessecacao, de cinzas totais, de cinzas insoluveis em acido, do indice de espuma, de substâncias extraiveis por alcool de acordo com procedimentos descritos na Farmacopeia Brasileira. Como tambem uma analise termica por termogravimetria (TG) e morfologica por Microscopia Eletronica de Varredura (MEV) apenas das folhas. Os pos das cascas e folhas foram classificados como moderadamente grosso e os testes farmacognosticos apresentaram teores aceitaveis. As imagens da droga vegetal (folhas adulta) revelaram particulas irregulares quanto ao tamanho e a forma. Um perfil termico tambem foi obtido para a droga vegetal. A caracterizacao da droga vegetal das folhas e cascas de T. gardneriana estabeleceu a padronizacao da materia-prima vegetal a ser utilizada no desenvolvimento de fitoterapicos, garantindo qualidade, reprodutibilidade e seguranca do material vegetal.

Os disturbios na secrecao do hormonio da insulina, pode levar a doencas hiperglicemiantes, tambem conhecidas como diabetes mellitus (DM) tipo 1, tipo 2 e DM gestacional. Como uma das principais causas de mortes, a DM e conhecida como uma Doenca Cronica Nao Transmissivel (DCNT). Dentre as plantas vegetais mais utilizadas pela industria farmaceutica para obtencao de novos principios ativos com acao terapeutica, se encontra a especie Libidibia ferrea . Distribuida em todas as regioes do Brasil, possui acao farmacologica diversa, principalmente, acao anti-hiperglicemiante. Essa atividade antidiabetica foi descoberta a partir da realizacao do extrato aquoso da casca do caule de L. ferrea submetido em ratos normoglicemicos , observando a presenca de taninos condensados e hidrolisaveis, uma vez que esses foram os compostos mais presentes no meio. Portanto, esse estudo teve como objetivo caracterizar fisico-quimicamente a droga vegetal, o extrato aquoso e o extrato seco do caule de L. ferrea para uma futura alternativa no tratamento de doencas hiperglicemiantes como a diabetes mellitus. As cascas do caule de L. ferrea foram coletadas no municipio de Pesqueira, Pernambuco, Brasil, e sua exsicata foi previamente identificada no Instituto Agronomico de Pernambuco (IPA). Em seguida, este material foi lavado e seco. Posteriormente, pulverizado, obtendo-se a droga vegetal (MPV) de L. ferrea. O extrato aquoso foi obtido atraves da infusao da droga vegetal em meio aquoso. Foram realizados os testes de determinacao do pH, densidade relativa e determinacao do residuo seco, onde todos os parâmetros analisados estavam dentro dos padroes exigidos pela Farmacopeia Brasileira 6a edicao. Em seguida, o extrato aquoso foi congelado para liofilizacao, obtendo-se o extrato seco de L. ferrea. Os resultados obtidos atraves da caracterizacao do extrato seco de L. ferrea atenderam aos parâmetros previamente estabelecidos.

Background: The development of antiretroviral associations in a single dosage form aims to ensure improved efficacy, low costs and better adherence to treatment. Objective: This work performed the pharmacotechnical development, coating, and stability studies of fixed-dose combination tablets of zidovudine, lamivudine and nevirapine (300 + 200 + 150 mg, respectively). Methods: Qualitative and quantitative planning of diluents (101 and 250 microcrystalline cellulose, spray-dried monohydrate lactose and corn starch) and coating polymers (Opadry white II HP® and Instacoat Aqua Moistshield II®) were analyzed, and direct compression (DC) and wet granulation (WG) methods were tested aiming the development of the pharmaceutical form. Quality control was carried out according to the specifications set by official compendia. The chosen formulation was scaled-up and the industrial batches were submitted to accelerated and long-term stability studies. Results: The batches obtained by WG met the requirements, using 101 microcrystalline cellulose, corn starch and Opadry white II HP® as excipients. The DC trial was not possible due to the need of a greater ratio of excipients to improve formulation properties. Conclusion: Thus, this study brings a new therapeutic alternative for HIV treatment, contributing to the development of another possibility to simplify drug administration.

Triplaris gardneriana is used by traditional medicine. The objective of this work was the leaves chemical study with isolate, identify and quantify the chemical constituent, validate the analytical method and evaluate the antibacterial activity. The ethyl acetate and chloroform fractions were subjected to column chromatography for isolation of the compounds quercetin and lupeol, respectively. For the identification, quantification of quercetin in the samples and validation of method were performed using HPLC-DAD. The antibacterial activity was evaluated by the microdilution method. The isolated phytochemicals are being reported for the first time in the species. The ethyl acetate fraction showed a higher content of quercetin with 9.967 ± 1.01 mg.g-1. The method was validated. The samples showed good antibacterial activity. In this study, quercetin was isolated and quantified in the species being a great alternative as a producer of this secondary metabolite, which can be safely applied in the quality control analysis.

The genus Mikania (Asteraceae) comprises about 450 species of these, 203 are found in Brazil and present several chemical and biological activities. Considering the variety of species and their therapeutic properties, the present study aimed to perform technological prospecting of this genus, since this approach aims to contribute to technological, scientific and innovation research. For this purpose, the patent documents were analyzed, regarding the applicant countries, year of filing and the international classification of patents of the genus Mikania. The search was conducted in the databases World Intellectual Property Organization (WIPO), European Patent Office (EPO) and the National Institute of Industrial Property (INPI) in October 2020, using the descriptor “Mikania”; present in the title and/or abstract in addition, documents that included medicinal approaches were selected. Thus, taking into consideration the filing countries, Japan, Brazil and the United States led the patent deposits, with the first document filed in 1991 and the largest number of applications in the years 2000 and 2010. The data concerning the international patent classification are concentrated in subclass A61K, which deals with preparations for medical, dental or hygienic purposes. These results demonstrated the therapeutic and technological potential of the Mikania species and thus which can be evidenced the potential of this study. El género Mikania (Asteraceae) comprende unas 450 especies, de las cuales 203 se encuentran en Brasil y presentan diversas actividades químicas y biológicas. Teniendo en cuenta la variedad de especies y sus propiedades terapéuticas, el presente estudio tuvo como objetivo realizar la prospección tecnológica de este género, ya que este enfoque pretende contribuir a la investigación tecnológica, científica y de innovación. Para ello, se analizaron los documentos de patentes, relativos a los países candidatos, el año de presentación y la clasificación internacional de patentes del género Mikania. La búsqueda se realizó en las bases de datos de la Organización Mundial de la Propiedad Intelectual (WIPO), la Oficina Europea de Patentes (EPO) y el Instituto Nacional de la Propiedad Industrial (INPI) en octubre de 2020, utilizando el descriptor "Mikania" presente en el título y/o el resumen, se seleccionaron los documentos que incluían enfoques medicinales. Así, teniendo en cuenta los países depositantes, Japón, Brasil y Estados Unidos lideraron la presentación de patentes, con el primer documento presentado en 1991 y el mayor número de solicitudes en los años 2000 y 2010. Los datos relativos a la clasificación internacional de patentes se concentran en la subclase A61K, que trata de las preparaciones para fines médicos, dentales o higiénicos. Estos resultados demostraron el potencial terapéutico y tecnológico de la especie Mikania, por lo que se puede evidenciar el potencial de este estudio. O gênero Mikania (Asteraceae) compreende cerca de 450 espécies, destas, 203 são encontradas no Brasil e apresentam várias atividades químicas e biológicas. Considerando a variedade de espécies e as suas propriedades terapêuticas, o presente estudo teve como objetivo realizar a prospecção tecnológica deste gênero, uma vez que esta abordagem visa contribuir para a investigação tecnológica, científica e de inovação. Para isto, foram analisados os documentos de patentes, relativos aos países candidatos, ano de depósito e a classificação internacional de patentes do gênero Mikania. A pesquisa foi conduzida nas bases de dados da Organização Mundial da Propriedade Intelectual (WIPO), Instituto Europeu de Patentes (EPO) e Instituto Nacional da Propriedade Industrial (INPI) em outubro de 2020, utilizando o descritor "Mikania" presente no título e/ou resumo, foram selecionados documentos que incluíam abordagens medicinais. Assim, levando em consideração os países depositários, Japão, Brasil e Estados Unidos lideraram os depósitos de patentes, com o primeiro documento depositado em 1991 e o maior número de pedidos nos anos 2000 e 2010. Os dados relativos à classificação internacional de patentes concentram-se na subclasse A61K, que trata de preparações para fins médicos, dentários ou higiênicos. Estes resultados demonstraram o potencial terapêutico e tecnológico da espécie Mikania e podem, assim, ser evidenciadas as potencialidades deste estudo.

The World Health Organization (WHO) classifies leishmaniasis as a disease for which the development of new treatments is a priority. Available drugs are not fully effective in all cases; they have parenteral administration and exhibit serious and common adverse effects. The only oral drug available (miltefosine) has shown resistance, is expensive, and is not available in many endemic countries. Thus, the development of an oral medicine may solve many of these issues. Based on that, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs for the treatment of cutaneous leishmaniasis. A literature search for keywords "leishmania and oral" was performed in PubMed and ScienceDirect, considering articles published in the last 5 years. The articles were selected based on the objective of the review. The main problem in the current treatment of leishmaniasis is the administration of injectables, since it requires patients to travel to health centers, hospitalization, and professional administration, conditions that are not adapted to the socioeconomic reality of patients. Therefore, many research studies have evaluated oral alternatives for the treatment of cutaneous leishmaniasis. The main tested approaches were obtaining new molecules, repositioning drugs, and new formulations of old drugs. The prospects are encouraging but still require more in vivo bioavailability and clinical trials.

Chagas disease is a neglected tropical disease caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi). Endemic in underdeveloped and developed countries, due to the migratory movement, it is considered a serious public health problem. Endemic in underdeveloped countries and due to the migratory movement, in developed countries as well, it is considered a serious public health problem. One of the reasons for this is a weak therapeutic arsenal, represented only by the drug benznidazole (BNZ) which, although it promotes significant cure rates in the acute phase of the disease, presents serious problems of toxicity and bioavailability, mainly due to its low aqueous solubility. Several studies have presented several drug delivery systems (DDS) based on BNZ aiming at enhancing its solubility in aqueous medium and, with this, promoting an increase in the dissolution rate and, consequently, in its bioavailability. However, the present work is a pioneer in using a zeolitic imidazolate framework as a carrier agent for a DDS in order to promote a pH-sensitive modulation of the drug. Thus, this work aimed to develop a novel DDS based on BNZ and the ZIF-8 to use it in development of prolonged-release dosage forms to alternative treatment of Chagas disease. The BNZ@ZIF-8 system was obtained through an ex situ method selected due to its higher incorporation efficiency (38%). Different characterization techniques corroborated the obtainment and drug release data were analyzed by in vitro dissolution assay under sink and non-sink conditions and setting the kinetic results through both model dependent and independent methods. Under sink conditions, at pH 4.5, BNZ and BNZ@ZIF-8 showed similar release profile, but the DDS was effective in promoting a prolonged release. At pH 7.6, after 7 h, BNZ showed a lower release than BNZ@ZIF-8. On the other hand, in non-sink conditions at pH 4.5 the BNZ presented 80% of drug release in 3 h, while the DDS in 6 h. At pH 7.6, BNZ presented a release of 80% in 2 h, while the DDS reaches it in only at 12 h. Therefore, at pH 4.5 the DDS BNZ@ZIF-8 showed a faster release with a burst effect, while at pH 7.6 it showed a prolonged and controlled release. Finally, it is evident that a promising DDS pH-sensitive was obtained as a novel carrier that might be able to prolongs BNZ release in dosage forms intended for the alternative treatment of Chagas disease.

This paper presents a software to build theoretical models of cyclodextrin derivatives and evaluate their host:guest interactions, using a graphical user interface in an intuitive way. This goal was outlined to facilitate the studies of molecular modeling, particularly from experimental groups with demands in this research field. The software (CycloMolder) consists of two modules: CycloGen and CycloDock. The first module builds theoretical models with more than one chemical structure to represent a cyclodextrin derivative. These structures are divided into configurations and conformations. The configurations can be homologous structures, with different molar substitution ratio, or just positional isomers. Conformers are generated from the built configurations. The second module performs the docking calculations between the host (cyclodextrins and/or their derivatives) and guest molecules, using the AutoDock Vina program, and displays the final results of the modeled inclusion complexes, including graphs showing the distribution energy and intermolecular interactions present in the host:guest complex.