Molecular Dynamics Simulations to Study Drug Delivery Systems

Molecular dynamics simulation is a very powerful tool to understand biomolecular processes. In this chapter, we go over different applications of this methodology to drug delivery systems (DDS) carried out in the group. DDS—a formulation or a device that enables the introduction of a therapeutic substance in the body and improves its efficacy and safety by controlling the rate, time, and place of release of drugs—are an important component of drug development and therapeutics. Biocompatible nanoparticles are materials in the nanoscale that emerged as important players, improving efficacy of approved drugs, for example. The molecular understanding of the encapsulation process could be very helpful to guide the nanocarrier for a specific system. Here we discuss different applications of drug delivery carriers, such as liposomes, polymeric micelles, and polymersomes using atomistic and coarse grain (CG) molecular dynamics simulations

MOÇO, O QUE TEM PRA LER? UM ESTUDO DO ACERVO PARA O PÚBLICO JUVENIL DA BIBLIOTECA PÚBLICA MUNICIPAL ANTÔNIO DIAS ANDRADE (ITABERABA/BA)

This article presents the results of a monographic study whose purpose was to analyze the collection of the Antônio Dias Andrade Municipal Public Library in the municipality of Itaberaba-BA with regard to materials for literary reading and adequacy of works aimed at young readers from Itaberaba. The methodology adopted for this was the documentary analysis of the collection of the library studied through the criteria for the composition of collections in public libraries established by the National Public Library System. The empirical study in question found that the collection aimed at the juvenile public of the Antônio Dias Andrade Municipal Public Library can be characterized as: science fiction, suspense narrative, fantastic elements (categories of collection composition); It has a very diversified collection with regard to literary typologies, namely: reference works, Brazilian literature, foreign literature, special materials, historical-documentary materials, children's literature. However, with regard to the collection aimed at the youth audience, it was noticed that the library is still very lacking in this regard, because when analyzing the entire bibliographic collection, it was observed that the library has only 10 books in its collection that can be categorized as juvenile literature and within other linguistic modalities regarding visual and sound materials, the library has materials that can be used by deaf and blind young people.O presente artigo apresenta os resultados de um estudo monográfico cujo propósito foi analisar o acervo da Biblioteca Pública Municipal Antônio Dias Andrade no que se refere aos materiais para leitura literária e adequação das obras voltadas para os leitores jovens Itaberabenses. A metodologia adotada para tal foi à análise documental do acervo da biblioteca estudada por meio dos critérios para composição de acervos em bibliotecas públicas estabelecidos pelo Sistema Nacional de Biblioteca Pública. O estudo empírico, em questão, constatou que o acervo voltado para o público juvenil da Biblioteca Pública Municipal Antônio Dias Andrade pode ser caracterizado como: ficção científica, narrativa de suspense, elementos fantásticos (categorias de composição de acervo); possui um acervo bem diversificado no que se refere às tipologias literárias, a saber: obras de referência, literatura brasileira, literatura estrangeira, materiais especiais, materiais histórico-documental, literatura infanto-juvenil. Porém, no que se refere ao acervo voltado para o público juvenil, percebeu-se que a biblioteca ainda é muito carente nesse quesito, pois ao analisar todo o acervo bibliográfico observou-se que a biblioteca possui somente 10 livros na sua coleção que podem ser categorizados como literatura juvenil e dentro de outras modalidades linguísticas no que tange a materiais de cunho visual e sonoro a biblioteca tem materiais que podem ser utilizados pelos jovens surdos e cegos

Effects of Gabaergic phenols on phospholipid bilayers as evaluated by 1H-NMR

The phenols propofol and thymol, and lately carvacrol, eugenol and chlorothymol, have been shown to act as positive allosteric modulators on GABAA receptor, which is the main inhibitory receptor of the central nervous system. GABAA receptor is an intrinsic membrane protein which activity may be affected by surface-active compounds and by physical changes in the membrane. Recently, we demonstrated that these phenols interacted with the lipid membrane phase, suggesting their anesthetic activity could be the combined result of their specific (with receptor proteins) as well as nonspecific (with surrounding lipid molecules) interaction modulating the supramolecular organization of the receptor environment. In the current study, by using 1H-NMR spectroscopy, we have investigated the effects of the insertion and the possible preferential location of the five phenol derivatives with GABAergic activity on EPC membranes. The results indicate that all compounds are able to insert in EPC phospholipid vesicles and to locate in the region between the polar group (choline molecule), the glycerol and the first atoms of the acyl chains, being the more lipophilic compounds (propofol and chlorothymol) that seem to prefer a deeper bilayer insertion. The location of the phenol molecules would reduce the repulsive forces among phospholipids head groups allowing closer molecular packing and finally diminishing the mobility of the hydrocarbon chains, as revealed by 1H spin relaxation times.Fil: Reiner, Gabriela de Las Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidade Estadual de Campinas; Brasil. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Fraceto, Leonardo Fernandes. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Paula, Eneida de. Universidade Estadual de Campinas; BrasilFil: Perillo, Maria Angelica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

Local anesthetics: interaction with human erythrocyte membranes as studied by ¹H and 31P nuclear magnetic resonance

The literature carries many theories about the mechanism of action of local anesthetics (LA). We can highlight those focusing the direct effect of LA on the sodium channel protein and the ones that consider the interaction of anesthetic molecules with the lipid membrane phase. The interaction between local anesthetics and human erythrocyte membranes has been studied by ¹H and 31P nuclear magnetic resonance spectroscopy. It was found that lidocaine (LDC) and benzocaine (BZC) bind to the membranes, increase the mobility of the protons of the phospholipid's acyl chains, and decrease the mobility and/or change the structure of the polar head groups. The results indicate that lidocaine molecules are inserted across the polar and liquid interface of the membrane, establishing both electrostatic (charged form) and hydrophobic (neutral form) interactions. Benzocaine locates itself a little deeper in the bilayer, between the interfacial glycerol region and the hydrophobic core. These changes in mobility or conformation of membrane lipids could affect the Na+-channel protein insertion in the bilayer, stabilizing it in the inactivated state, thus causing anesthesia.6671Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Physicochemical stability of poly(lactide-co-glycolide) nanocapsules containing the local anesthetic Bupivacaine

This paper describes the preparation of poly(DL-lactide-co-glicolide) (PLGA) nanocapsules as a drug carrier system for the local anesthetic bupivacaine. The system was characterized and its stability investigated. The results showed a size distribution with a polydispersity index of 0.12, an average diameter of 148 nm, a zeta potential of -43.5 mV and an entrapment efficiency of 75.8%. The physicochemical properties of polymeric nanocapsule suspensions (average diameter, polydispersity, zeta potential and drug association efficiency) were evaluated as a function of time to determine the formulation stability. The formulation did not display major changes in these properties over the time, and it was considered stable up to 120 days of storage at room temperature. The results reported here which refer to the initial characterization of these new formulations for the local anesthetic bupivacaine show a promising potential for future in vivo studies.Neste trabalho foi realizada a preparação de nanocápsulas de poli (DL-lactídeo-co-glicolídeo) (PLGA) como um sistema carreador para o anestésico local bupivacaína. A preparação foi caracterizada e sua estabilidade físico-química avaliada. Os resultados da caracterização mostram uma distribuição de tamanho com um índice de polidispersão de 0,12, um diâmetro médio de 148 nm, um potencial zeta de -43,5 mV e uma eficiência de associação da BVC nas nanocápsulas de 75,8%. As propriedades físico-químicas das suspensões (diâmetro hidrodinâmico, índice de polidispersão, potencial zeta e eficiência de associação do fármaco) contendo nanocápsulas poliméricas foram avaliadas em função do tempo a fim de determinar sua estabilidade. Nenhuma grande alteração foi observada em função tempo para as suspensões de nanocápsulas avaliadas, sendo consideradas estáveis por um período de armazenagem de 120 dias a temperatura ambiente. Os resultados aqui apresentados, os quais se referem ao estudo desta nova formulação para anestésico local bupivacaína mostram-se promissores para futuros estudos in vivo.9951000Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação para o Desenvolvimento da UNESP (FUNDUNESP

Direct Visualization of the Action of Triton X-100 on Giant Vesicles of Erythrocyte Membrane Lipids

The raft hypothesis proposes that microdomains enriched in sphingolipids, cholesterol, and specific proteins are transiently formed to accomplish important cellular tasks. Equivocally, detergent-resistant membranes were initially assumed to be identical to membrane rafts, because of similarities between their compositions. in fact, the impact of detergents in membrane organization is still controversial. Here, we use phase contrast and fluorescence microscopy to observe giant unilamellar vesicles (GUVs) made of erythrocyte membrane lipids (erythro-GUVs) when exposed to the detergent Triton X-100 (TX-100). We clearly show that TX-100 has a restructuring action on biomembranes. Contact with TX-100 readily induces domain formation on the previously homogeneous membrane of erythro-GUVs at physiological and room temperatures. the shape and dynamics of the formed domains point to liquid-ordered/liquid-disordered (Lo/Ld) phase separation, typically found in raft-like ternary lipid mixtures. the Ld domains are then separated from the original vesicle and completely solubilized by TX-100. the insoluble vesicle left, in the Lo phase, represents around 2/3 of the original vesicle surface at room temperature and decreases to almost 1/2 at physiological temperature. This chain of events could be entirely reproduced with biomimetic GUVs of a simple ternary lipid mixture, 2:1:2 POPC/SM/chol (phosphatidylcholine/sphyngonnyelin/cholesterol), showing that this behavior will arise because of fundamental physicochemical properties of simple lipid mixtures. This work provides direct visualization of TX-100-induced domain formation followed by selective (Ld phase) solubilization in a model system with a complex biological lipid composition.Brazilian Research foundationsFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)TNCT-FaxCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Estadual Campinas, Inst Biol, Dept Bioquim, Campinas, SP, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilFAPESP: 2009/0904-1FAPESP: 2012/10442-8FAPESP: 2010/18516-5CNPq: 479993/2011-4CNPq: 472054/2011-2Web of Scienc

X‐Ray Scattering Techniques Applied in the Development of Drug Delivery Systems

The advances in nanotechnology have found application in different fields, such as food, agriculture, materials, chemistry, and medicine. However, one of the most important approaches is the development of nanocarriers and, in order to understand their structural organization, different physicochemical techniques have been used. In particular, small angle X‐ray scattering (SAXS) and X‐ray diffraction (XRD) have given important contribution to the study of organization phase of nanocarriers such as organic/inorganic nanoparticles, micelles, liposomes, cyclodextrins, polymers, and their interaction with drugs and other bioactive molecules. In this chapter, we will present theoretical aspects, experimental design, and the applications of both techniques for the development of delivery systems for bioactive molecules

Gestão da Informação científica: o Portal de periódicos da Universidade Federal do Rio de Janeiro

It shows that journal articles, as a source of scientific information, are fundamental in universities. The light of information technologies, the number of periodicals in electronic media grows. UFRJ, as a major knowledge producer, regularly publishes 55 titles in several areas of knowledge, in a fragmented and dispersed way, making it difficult for the community to absorb it and the global knowledge of its production. The System of Libraries and Information (SiBI), with the objective of identifying, gathering and disseminating current, electronic and printed periodicals, published at UFRJ in its various fields of activity, created the "UFRJ Portal of Periodicals" -www.portaldeperiodicos.sibi .ufrj.br. This measure, in addition to providing visibility to the titles, disseminates academic production in an organized way, reflects the wide and interesting diversity of UFRJ research lines, registered in the form of periodical articles.Evidencia que os artigos de periódicos, como fonte de informação científica, são fundamentais nas universidades. A luz das tecnologias da informação, cresce o número de publicações periódicas em meio eletrônico. A UFRJ, como grande produtora de conhecimento edita regularmente 55 títulos em diversas áreas do conhecimento, de forma fragmentada e dispersa, dificultando sua absorção por toda a comunidade e o conhecimento global de sua produção. O Sistema de Bibliotecas e Informação (SiBI) com o objetivo de identificar, reunir e divulgar os periódicos correntes, eletrônicos e impressos, editados na UFRJ em seus diversos campos de atuação criou o “Portal de Periódicos da UFRJ”-www.portaldeperiodicos.sibi.ufrj.br. Essa medida, além de propiciar uma visibilidade aos títulos, divulgar a produção acadêmica de forma organizada, reflete a ampla e interessante diversidade das linhas de pesquisa da UFRJ, registradas sob a forma de artigos de periódicos

Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal Cells

Articaine (ATC) and lidocaine (LDC) are the local anesthetics (LAs) currently most employed in dentistry. Cases of paresthesia, reported more frequently for ATC, have raised concerns about their potential neurotoxicity, calling for further investigation of their biological effects in neuronal cells. In this work, the impact of ATC and LDC on the metabolism of SH-SY5Y cells was investigated through 1H NMR metabolomics. For each LA, in vitro cultured cells were exposed to concentrations causing 10 and 50% reductions in cell viability, and their metabolic intracellular and extracellular profiles were characterized. Most effects were common to ATC and LDC, although with varying magnitudes. The metabolic variations elicited by the two LAs suggested (i) downregulation of glycolysis and of glucose-dependent pathways (e.g., one-carbon metabolism and hexosamine biosynthetic pathway), (ii) disturbance of branched chain amino acids (BCAA) catabolism, (iii) downregulation of TCA cycle anaplerotic fueling and activation of alternative energy producing pathways, (iv) interference with choline metabolism and (v) lipid droplet build-up. Interestingly, LDC had a greater impact on membrane phospholipid turnover, as suggested by higher phosphatidylcholine to phosphocholine conversion. Moreover, LDC elicited an increase in triglycerides, whereas cholesteryl esters accumulated in ATC-exposed cells, suggesting a different composition and handling of lipid droplets.publishe