RESUMO
l-Asparaginase (ASNase) is an amidohydrolase used as a chemotherapeutic agent for the treatment of acute lymphoblastic leukemia (ALL). The nanoencapsulation of this enzyme is strategic to avoid its immediate immunogenic effects that lead to a decrease in the enzyme half-life. In this work, ASNase-containing nanoparticles (NPs) were prepared by double emulsification, through an ultrasonic sonicator or an Ultra-Turrax, using two copolymers of 50:50 (w/w) poly (lactic-co-glycolic acid) (PLGA) with different ranges of molecular weight (24-38â¯kDa and 30-60â¯kDa) and varying the concentration of polyvinyl alcohol (PVA) as a stabilizer (0.5, 1.0, 1.5 and 2.0%) as well as the emulsification time (30 and 60â¯s). Using 24-38â¯kDa PLGA and 1.0% PVA, we obtained by cavitation NPs with hydrodynamic diameter of 384â¯nm, polydispersity index of 0.143 and Zeta potential of -16.4â¯mV, whose ASNase encapsulation efficiency was as high as 87⯱â¯2%. The encapsulated enzyme showed an activity 22% higher than that of the free enzyme, and no conformational changes were detected by circular dichroism. The enzyme release from NPs entrapped in dialysis bags (500â¯kDa molecular weight cut-off) allowed selecting a controlled system able to release about 60% of the enzyme within 14â¯days, for which the Korsmeyer-Peppas model provided the best correlation (R2â¯=â¯0.966).
Assuntos
Asparaginase/metabolismo , Nanosferas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Emulsões/química , Estabilidade Enzimática , Enzimas Imobilizadas/metabolismo , Hemólise , Hidrodinâmica , Nanosferas/ultraestrutura , OvinosRESUMO
Hemoglobin variants (Hb) result from mutations in globin genes, with amino acid substitution in the polypeptide chain. Among the most common structural variants are HbS, HbC, HbD and HbE. The S hemoglobin gene is a high frequency gene across America and Brazil, where it is more frequent in the Southeast and Northeast. The scope of this article is to investigate the presence of hemoglobin variants in 15 quilombos (fugitive slave communities) of Piaui. The sample was of 1,239 people and hemoglobin was screened by high-performance liquid chromatography (HPLC). A questionnaire was applied related to gender, ethnicity and consanguinity. Of the samples analyzed, 5.4% had AS sickle cell trait, while SS and SC sickle cell anemia showed a rate of 0.8%, with AC, AD and DD hemoglobin. Of the 1,069 Afro-descendants, 84 revealed hemoglobin abnormalities, 34 being male 53 being female. There were 13 consanguineous marriages among the 84 hemoglobin alterations. The study of hemoglobin variants in 15 former quilombo communities in the state of Piaui contributes to their education in health in the aspects of genetic inheritance of hemoglobin, a relevant public health issue, providing input for the implementation of the State Program of Sickle Cell Disease of Piaui.
As hemoglobinas variantes (Hb) decorrem de mutações nos genes da globina. As variantes estruturais mais frequentes são HbS, HbC, HbD e HbE. O gene da hemoglobina S tem frequência elevada na América, enquanto que no Brasil é maior no Sudeste e Nordeste. O presente artigo tem por objetivo investigar a presença de hemoglobinas variantes em 15 comunidades quilombolas do estado do Piauí. Foram analisadas 1.239 amostras, nas quais as hemoglobinas foram triadas pela cromatografia líquida de alta eficiência (HPLC). Aplicou-se questionário referente a gênero, etnia e consanguinidade das populações. Das 1.239 amostras, 5,4% apresentaram o traço falciforme AS, as doenças falciformes SS e SC apareceram em 0,8% do total, nas hemoglobinas AC, AD e DD. Das 1.069 pessoas negras, 84 apresentaram alteração das hemoglobinas; destas, 34 eram do sexo masculino e 53 do feminino. Ocorreu a presença de 13 casamentos consanguíneos dentre as 84 alterações das hemoglobinas. O estudo das hemoglobinas variantes em 15 comunidades remanescentes de quilombos do Piauí contribui para sua educação em saúde frente aos aspectos da herança genética destas proteínas, relevante questão de saúde pública, proporcionando subsídios para a implantação do Programa Estadual da Doença Falciforme do Piauí.
Assuntos
Anemia Falciforme/epidemiologia , Etnicidade/genética , Hemoglobinas/genética , Traço Falciforme/epidemiologia , Substituição de Aminoácidos/genética , Anemia Falciforme/genética , População Negra/genética , Brasil/epidemiologia , Cromatografia Líquida de Alta Pressão/métodos , Consanguinidade , Feminino , Frequência do Gene , Variação Genética , Humanos , Masculino , Prevalência , Traço Falciforme/genética , Inquéritos e QuestionáriosRESUMO
Resumo As hemoglobinas variantes (Hb) decorrem de mutações nos genes da globina. As variantes estruturais mais frequentes são HbS, HbC, HbD e HbE. O gene da hemoglobina S tem frequência elevada na América, enquanto que no Brasil é maior no Sudeste e Nordeste. O presente artigo tem por objetivo investigar a presença de hemoglobinas variantes em 15 comunidades quilombolas do estado do Piauí. Foram analisadas 1.239 amostras, nas quais as hemoglobinas foram triadas pela cromatografia líquida de alta eficiência (HPLC). Aplicou-se questionário referente a gênero, etnia e consanguinidade das populações. Das 1.239 amostras, 5,4% apresentaram o traço falciforme AS, as doenças falciformes SS e SC apareceram em 0,8% do total, nas hemoglobinas AC, AD e DD. Das 1.069 pessoas negras, 84 apresentaram alteração das hemoglobinas; destas, 34 eram do sexo masculino e 53 do feminino. Ocorreu a presença de 13 casamentos consanguíneos dentre as 84 alterações das hemoglobinas. O estudo das hemoglobinas variantes em 15 comunidades remanescentes de quilombos do Piauí contribui para sua educação em saúde frente aos aspectos da herança genética destas proteínas, relevante questão de saúde pública, proporcionando subsídios para a implantação do Programa Estadual da Doença Falciforme do Piauí.
Abstract Hemoglobin variants (Hb) result from mutations in globin genes, with amino acid substitution in the polypeptide chain. Among the most common structural variants are HbS, HbC, HbD and HbE. The S hemoglobin gene is a high frequency gene across America and Brazil, where it is more frequent in the Southeast and Northeast. The scope of this article is to investigate the presence of hemoglobin variants in 15 quilombos (fugitive slave communities) of Piaui. The sample was of 1,239 people and hemoglobin was screened by high-performance liquid chromatography (HPLC). A questionnaire was applied related to gender, ethnicity and consanguinity. Of the samples analyzed, 5.4% had AS sickle cell trait, while SS and SC sickle cell anemia showed a rate of 0.8%, with AC, AD and DD hemoglobin. Of the 1,069 Afro-descendants, 84 revealed hemoglobin abnormalities, 34 being male 53 being female. There were 13 consanguineous marriages among the 84 hemoglobin alterations. The study of hemoglobin variants in 15 former quilombo communities in the state of Piaui contributes to their education in health in the aspects of genetic inheritance of hemoglobin, a relevant public health issue, providing input for the implementation of the State Program of Sickle Cell Disease of Piaui.
Assuntos
Humanos , Masculino , Feminino , Traço Falciforme/epidemiologia , Hemoglobinas/genética , Etnicidade/genética , Anemia Falciforme/epidemiologia , Traço Falciforme/genética , Variação Genética , Brasil/epidemiologia , Prevalência , Inquéritos e Questionários , Cromatografia Líquida de Alta Pressão/métodos , Consanguinidade , Substituição de Aminoácidos/genética , Negro ou Afro-Americano/genética , Frequência do Gene , Anemia Falciforme/genéticaRESUMO
This study proposed to investigate and to compare colloidal carrier systems containing Zidovudine (3'-azido-3'-deoxythymidine) (AZT) for transdermal administration and optimization of antiretroviral therapy. Microemulsion (ME) and lamellar phase (LP) liquid crystal were obtained and selected from pseudoternary diagrams previously developed. Small-angle X-ray scattering and rheology analysis confirmed the presence of typical ME and liquid crystalline structures with lamellar arrangement, respectively. Both colloidal carrier systems, ME, and LP remained stable, homogeneous, and isotropic after AZT addition. In vitro permeation study (using pig ear skin) showed that the amount of permeated drug was higher for ME compared to the control and LP, obtaining a permeation enhancing effect on the order of approximately 2-fold (p < 0.05). Microscopic examination after in vivo skin irritation studies using mice suggested few histological changes in the skin of animals treated with the ME compared to the control group (hydrogel). Thus, ME proved to be adequate and have promising effects, being able to promote the drug permeation without causing apparent skin irritation. On the order hand, LP functioned as a drug reservoir reducing AZT partitioning into the skin.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Sistemas de Liberação de Medicamentos , Zidovudina/administração & dosagem , Administração Cutânea , Animais , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Emulsões , Feminino , Hidrogéis , Irritantes , Cristais Líquidos , Camundongos , Nanotecnologia , Espalhamento de Radiação , Absorção Cutânea , Suínos , Raios X , Zidovudina/efeitos adversos , Zidovudina/farmacocinéticaRESUMO
ABSTRACT This study aimed to obtain and characterize a microemulsion (ME) containing phenobarbital (PB). The PB was incorporated in the proportion of 5% and 10% in a microemulsion system containing Labrasol(r), ethanol, isopropyl myristate and purified water. The physicochemical characterization was performed and the primary stability of the ME was evaluated. An analytical method was developed using spectrophotometry in UV = 242 nm. The kinetics of the in vitro release (Franz model) of the ME and the emulsion (EM) containing PB was evaluated. The incorporation of PB into ME at concentrations of 5 and 10% did not change pH and resistance to centrifugation. There was an increase in particle size, a decrease of conductivity and a change in the refractive index in relation to placebo ME. The ME remained stable in preliminary stability tests. The analytical method proved to be specific, linear, precise, accurate and robust. Regarding the kinetics of the in vitro release, ME obtained an in vitro release profile greater than the EM containing PB. Thus, the obtained ME has a potential for future transdermal application, being able to compose a drug delivery system for the treatment of epilepsy.
RESUMO O objetivo deste trabalho foi obter e caracterizar uma microemulsão (ME) contendo fenobarbital (FEN). O FEN foi incorporado na proporção de 5% e 10% em um sistema microemulsionado composto por labrasol(r), etanol, miristato de isopropila e água purificada. Foi realizada a caracterização físico-química e avaliada a estabilidade preliminar da ME. Desenvolveu-se um método analítico por espectrofotometria em UV = 242 nm. Foi avaliada a cinética de liberação in vitro (em modelo de Franz) da ME e da emulsão (EM) contendo FEN. A incorporação do FEN em ME nas concentrações de 5 e 10% não alterou o pH e a resistência à centrifugação. Houve aumento do tamanho da partícula, redução da condutividade e alteração do índice de refração em relação à ME placebo. A ME manteve-se estável nos ensaios de estabilidade preliminar. O método analítico demonstrou ser específico, linear, preciso, exato e robusto. Na cinética de liberação in vitro, a ME obteve um perfil de liberação in vitro superior a EM contendo FEN. Desta forma, a ME obtida tem potencial para uma futura aplicação transdérmica, podendo compor um sistema de liberação de fármacos para tratamento da epilepsia.
Assuntos
Fenobarbital/farmacocinética , Emulsões/análise , Controle de Qualidade , Espectrofotometria Ultravioleta/métodos , Cinética , Nanotecnologia/métodos , Liberação Controlada de Fármacos/efeitos dos fármacosRESUMO
Fungal infections have become a major problem of worldwide concern. Yeasts belonging to the Candida genus and the pathogenic fungus Cryptococcus neoformans are responsible for different clinical manifestations, especially in immunocompromised patients. Antifungal therapies are currently based on a few chemotherapeutic agents that have problems related to effectiveness and resistance profiles. Microemulsions are isotropic, thermodynamically stable transparent systems of oil, water and surfactant that can improve the solubilization of lipophilic drugs. Taking into account the need for more effective and less toxic drugs along with the potential of thiophene derivatives as inhibitors of pathogenic fungi growth, this study aimed to evaluate the antifungal activity of a thiophene derivative (5CN05) embedded in a microemulsion (ME). The minimum inhibitory concentration (MIC) was determined using the microdilution method using amphotericin B as a control. The formulations tested (ME- blank and ME-5CN05) showed physico-chemical properties that would allow their use by the topical route. 5CN05 as such exhibited moderate or weak antifungal activity against Candida species (MIC = 270-540 µg.mL-1) and good activity against C. neoformans (MIC = 17 µg.mL-1). Candida species were susceptible to ME-5CN05 (70-140 µg.mL-1), but C. neoformans was much more, presenting a MIC value of 2.2 µg.mL-1. The results of this work proved promising for the pharmaceutical industry, because they suggest an alternative therapy against C. neoformans.
Assuntos
Anti-Infecciosos Locais/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Emulsões/farmacologia , Tiofenos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Como parte integrante do conjunto de normas das boas práticas de fabricação de medicamentos, a validação de limpeza visa demonstrar a garantia da remoção de resíduos de produtos recém-fabricados, evitando a contaminação cruzada. Neste trabalho, apresenta-se uma estratégia para validação de limpeza de formas farmacêuticas sólidas, manipuladas por granulação úmida. Para tanto, foi escolhido a furosemida, um fármaco de ação diurética, apresentado na forma de comprimidos e produzido pelo Lafepe® (Recife-PE, Brasil). Para análise dos resíduos do fármaco, a coleta das amostras foi realizada por swab e os métodos de quantificação utilizados foram por espectrofotometria e por cromatografia líquida de alta eficiência, este último foi desenvolvido e validado pelo Lafepe®. Na detecção de resíduos de produtos de limpeza, a amostragem foi realizada por água de enxágüe, analisando o pH e a condutividade. O limite de aceitação da limpeza do princípio ativo foi de 8,26 miug mL-1 de furosemida no produto subseqüente e do detergente nos equipamentos foi de 10 ppm. Por conseguinte, observou-se que os resíduos dos contaminantes encontrados nos equipamentos após a limpeza foram inferiores aos limites de aceitação admitidos, o que assevera a eficácia e segurança da limpeza realizada na empresa.
As an integral part of the set of good practices in medicine fabrication, the purpose of cleaning validation is to guarantee the removal of remains of newly manufactured products and thus avoid cross-contamination. This article presents an approach to cleaning validation for the compounding of solid pharmaceutical forms by wet granulation. The method is demonstrated for furosemide, a diuretic drug, fabricated in the form of tablets by Lafepe® (Recife, PE, Brazil), in a multipurpose production line. To analyze drug residues left in the equipment after cleaning, samples were collected from surfaces by swab and traces of furosemide were quantitated by spectrophotometry and by a high performance liquid chromatography method developed and validated at the Lafepe® laboratories. To detect residues of detergent used in cleaning, the pH and conductivity of the final rinsing water were measured and compared with those of known dilutions. The acceptance cleaning limit of the active principle was 8.26 miug mL-1 of furosemide in the subsequent product and for the detergent it was 10 ppm in the last rinse of the equipment. The results showed that the residues of contaminants found in the equipment after cleaning were below the acceptable limits, which certifies the effectiveness and security of the cleaning practices in this company.
