Nanopartículas superparamagnéticas encapsuladas com polímeros para tratamento de câncer por hipertermia

O câncer é uma das maiores causas de mortalidade no Brasil e no mundo, com potencial de crescimento nas próximas décadas. Um tipo de tratamento promissor é a hipertermia magnética, procedimento no qual as células tumorais morrem pelo efeito do calor gerado por partículas magnéticas após a aplicação de campo magnético alternado em frequências adequadas. Tais partículas também são capazes de atuar como agentes de contraste para imageamento por ressonância magnética, um poderoso método de diagnóstico para identificação de células neoplásicas, formando a combinação conhecida como theranostics (terapia e diagnóstico). Neste trabalho foram sintetizadas nanopartículas de óxido de ferro por método de coprecipitação com posterior encapsulação por técnica de nano spray drying, visando sua aplicação no tratamento de câncer por hipertermia e como agente de contraste para imageamento por ressonância magnética. Para a encapsulação foram utilizadas matrizes poliméricas de Maltodextrina com Polissorbato 80, Pluronic F68, Eudragit® S100 e PCL com Pluronic F68, escolhidos com o intuito de formar partículas que dispersem bem em meio aquoso e que consigam atingir alvo tumoral após administração no corpo do paciente. Parâmetros de secagem pelo equipamento Nano Spray Dryer, como temperatura, solvente e concentração de reagentes, foram avaliados. As partículas formadas foram caracterizadas por Microscopia Eletrônica de Varredura, Difração de Raios-X, Análise Termogravimétrica, Espalhamento de Luz Dinâmico, Espectroscopia de Infravermelho, magnetismo quanto a magnetização de saturação e temperatura, citotoxicidade e potencial de aquecimento. Tais procedimentos indicaram que o método de coprecipitação produziu nanopartículas de magnetita de tamanho em torno 20 nm, superparamagnéticas a temperatura ambiente, sem potencial citotóxico. A técnica de nano spray drying foi eficiente para a formação de partículas com tamanho em torno de 1 μm, também superparamagnéticas, biocompatíveis e com propriedades magnéticas adequadas e para aplicações pretendidas. Destaca-se a amostra com Pluronic, OF-10/15-1P, que apresentou magnetização de saturação de 68,7 emu/g e interação específica com células tumorais.

Otimização da inativação fotodinâmica de E. coli por fotossensibilizadores veiculados por nanopartículas de sílica

A nanotecnologia tem sido aplicada para o desenvolvimento de materiais para diversas aplicações inclusive na inativação de patógenos. As nanopartículas de sílica (npSi) destacam-se pela alta área superficial, facilidade na alteração da superfície para aumento da eficiência adsortiva, penetrabilidade e toxicidade para bactérias gram-negativas sendo biocompatíveis para células de mamíferos e mais foto-estáveis que a maioria dos compostos orgânicos. Devido as suas vantagens, as npSi podem ser usadas para veicular fotossensibilizadores (FSs) uma vez que permitem sua utilização em solução aquosa em que os FSs geralmente são insolúveis. Além disso, o uso de FSs em vez de antibióticos, permite a inativação microbiológica pela Terapia Fotodinâmica sem que as bactérias adquiram resistência por mecanismos genéticos. Esse processo ocorre pela interação entre um FS, luz e oxigênio molecular produzindo oxigênio singleto que é extremamente reativo danificando estruturas celulares. O objetivo desse estudo foi otimizar a fotoinativação dinâmica de E .coli utilizando Azul de Metileno (AM) e Azul de Toluidina O (ATO) veiculados por npSi. As npSi foram preparadas pela metodologia sol-gel, caracterizadas por microscopia eletrônica de varredura (MEV) e submetidas à adsorção de AM e ATO em sua superfície. A presença de AM e ATO na superfície das npSi foram analisadas por espectroscopia no infravermelho; espectroscopia de fluorescência por raio-X e análise termogravimétrica. O planejamento experimental, iniciado pelo fatorial 23 e modelado ao composto central em busca das condições ótimas foi adotado pela primeira vez nessa aplicabilidade, visando a fotoinativação de E. coli empregando AM e ATO em solução e em seguida com npSi. AM e ATO veiculados por npSi permitem a fotoinativação em concentrações mais baixas de FS (20 e 51% respectivamente), causando desestruturação da integridade bacteriana demonstrada por MEV. Os resultados sugerem que a veiculação de AM e ATO por npSi é extremamente efetiva para a fotoinativação dinâmica de E. coli e que o planejamento composto central pode levar à completa inativação das bactérias.

Estudo de nanocompósitos formados por PLA e nanopartículas de celulose.

Devido à preocupação com o meio ambiente e o volume crescente de resíduos plástico em aterros sanitários, os polímeros biodegradáveis estão sendo estudados extensivamente. Um deles é o PLA. Apesar de possuir propriedades comparáveis a polímeros commodities e polímeros de engenharia, ainda é necessário melhorar certas características do PLA, como resistência ao impacto. Para isso, a nanocelulose (NC) pode ser usada sem alterações significativas na biodegradação polimérica. Este estudo teve como objetivo obter a nanocelulose, caracteriza-la e incorpora-la ao poli(ácido láctico) (PLA), assim como, estudar as propriedades térmicas, morfológicas e mecânicas do compósito obtido. A NC foi obtida por hidrólise ácida utilizando ácido fosfórico e posteriormente foi silanizada com três silanos distintos. As nanopartículas foram caracterizadas por Birrefringência, Microscopia Eletrônica de Transmissão (MET), Termogravimetria (TG), Potencial Zeta, Espectroscopia Vibracional de Absorção no Infravermelho com Transformada de Fourier (FTIR) e Difração de Raio X (DRX). Com as imagens obtidas pelo MET foi possível medir o tamanho das partículas de NC. E então obter a razão de aspecto de 82 e o limite de percolação de 1,1% em massa, confirmando a morfologia de nanofibra. De acordo as analises TG\'s, a presença de NC silanizada aumentou o início da degradação térmica. Os compósitos, contendo 3% em massa de NC, foram obtidos por fusão em câmara de mistura e moldados por injeção. Os compósitos foram caracterizados por FTIR, Cromatografia de Permeação em Gel (GPC), TG, Calorimetria Exploratória Diferencial (DSC), Microscopia Eletrônica de Varredura (MEV-FEG), Impacto e Tração. As análises dos compósitos mostraram que a NC atuou como agente de nucleação, facilitando a cristalização do PLA, além de a NC ter atuado como reforço na matriz polimérica melhorando as propriedades mecânicas.

Utilização de açúcares em nanopartículas para a veiculação de fármacos

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Preparação e caracterização de micro/nanopartículas de quitosano para libertação de cisplatina

Nos últimos anos, a crescente necessidade de desenvolvimento de novos e inovadores sistemas para a libertação de fármacos, tem levado a comunidade científica à pesquisa de novos materiais, maioritariamente de origem polimérica. O aparecimento destes materiais abre novas possibilidades aos campos de investigação da medicina e farmacologia, uma vez que os polímeros podem ser facilmente modificados (por reticulação física ou química) e processados nas mais diversas formas. Entre os novos materiais estudados encontra-se o quitosano, um polímero de origem natural extraído das carapaças de animais marinhos. O quitosano tem sido exaustivamente investigado devido a um conjunto de características, como biocompatibilidade, biodegradabilidade e ausência de toxicidade. O objectivo do presente trabalho consiste na preparação de microsferas de quitosano pelo método de emulsão água-em-óleo, seguido de reticulação, para utilização como sistemas de libertação de fármacos. Após análise da literatura disponível, verifica-se que existe um hiato de informação sobre o impacto das condições iniciais da preparação de microsferas nas suas características de tamanho e forma, pelo que se considerou importante colmatar a presente falta com este estudo, uma vez que o conhecimento da morfologia das microsferas preparadas é fulcral para estudos de difusão. Em estudos de libertação de fármacos, o quitosano geralmente apresenta elevadas taxas de difusão e biodegradação, juntamente com reduzidas propriedades mecânicas. Na tentativa de melhorar estas propriedades, as microsferas de quitosano são reticuladas quimicamente com genipin, um reticulante de origem natural. Para o estudo do impacto das variáveis de entrada no tamanho e na morfologia das microsferas, variou-se a concentração de quitosano, a concentração de genipin e a velocidade de agitação da emulsão água-em-óleo, pois na informação existente na literatura está patente que estas são as variáveis mais relevantes. Depois de obtidas as microsferas, foram recolhidas imagens com uma camara de alta resolução acoplada a um microscópio óptico, sendo que a dimensão e a morfologia destas foi analisada por análise de imagem, com recurso ao software de imagem ImageJ®. Foram medidos os parâmetros de tamanho, designadamente o diâmetro equivalente, o perímetro e os diâmetros de Feret (máximo e mínimo), e os parâmetros de forma: a circularidade e o factor de forma (AR). Os resultados obtidos mostram que o diâmetro equivalente das microsferas de quitosano reticuladas com genipin (bem como todas as restantes propriedades de tamanho) diminui com a diminuição quer da concentração de polímero quer da concentração de reticulante. O aumento da velocidade de agitação da emulsão também se reflecte numa diminuição da dimensão das microsferas. As variáveis de entrada não aparentam ter qualquer tipo de impacto sobre as características de forma, embora os resultados indiciem que as microsferas mais pequenas, de menor diâmetro equivalente são as que, aparentemente, apresentam maior esfericidade. Estes resultados, de natureza qualitativa, foram consolidados por recurso a Análise de Variância (ANOVA)

Síntese e imobilização de nanopartículas de ouro em fibras regeneradas via exaustão para potencial aplicação biomédica

The advancement of nanotechnology in the synthesis and characterisation of nanoparticles (NP's) has played an important role in the development of new technologies for various applications of nano-scale materials that have unique properties. The scientific development in the last decades in the field of nanotechnology has sought ceaselessly, the discovery of new materials for the most diverse applications, such as biomedical areas, chemical, optical, mechanical and textiles. The high bactericidal efficiency of metallic nanoparticles (Au and Ag), among other metals is well known, due to its ability to act in the DNA of fungi, viruses and bacteria, interrupting the process of cellular respiration, making them important means of study, in addition to its ability to protect UVA and UVB. The present work has as its main objective the implementation of an innovative method in the impregnation of nanoparticles of gold in textile substrate, functionalized with chitosan, by a dyeing process by exhaustion, with the control of temperature, time and velocity, thus obtaining microbial characteristics and UV protection. The exhausted substrates with colloidal solutions of NPAu's presented the colours, lilac and red (soybean knits) due to their surface plasmon peak around 520-540 nm. The NPAu's were synthesized chemically, using sodium citrate as a reducing agent and stabilizer. The material was previously cationised with chitosan, a natural polyelectrolyte, with the purpose of functionalising it to enhance the adsorption of colloid, at concentrations of 5, 7, 10 and 20 % of the bonding agent on the weight of the material (OWM). It was also observed, through an experimental design 23 , with 3 central points, which was the best process of exhaustion of the substrates, using the following factors: Time (min.), temperature (OC) and concentration of the colloid (%), having as a response to variable K/S (ABSORBÂNCIA/ Kubelka-Munk) of the fibres. Furthermore, it was evidenced as the best response, the following parameters: concentration 100%, temperature 70 ºC and time 30 minutes. The substrate with NPAu was characterised by XRD; thermal analysis using TGA; microstructural study using SEM/EDS and STEM, thus showing the NP on the surface of the substrate confirming the presence of the metal. The substrates showed higher washing fastness, antibacterial properties and UV radiation protection.

Micropartículas contendo nanopartículas de quitosana usando sulfato e genipina para liberação modificada da triancinolona: obtenção, caracterização e estudo em células tumorais

Chitosan is a polymer biocompatibility and biodegradability widely used in drug delivery systems. The co-crosslinking of chitosan with sodium sulfate and genipin, to form particulate systems is related of making them more resistant to acidic pH and to modulate the release kinetics for the oral route. Triamcinolone is a glucocorticoid with anti-inflammatory and immunosuppressive actions. The nanoparticles were prepared by co-crosslinking and characterized for particle size, PDI, zeta potential, crosslinking degree, encapsulation rate, morphology, infrared spectroscopy, thermal analysis, release kinetics and cells studies. The nanoparticles were prepared initially without genipin with sodium sulphate and the particles parameters were monitored in function of different ratio of drug / polymer, different concentrations of sodium sulfate and polysorbate 80 and the drip mode of crosslinkers on polymers. After optimizing conditions, the chosen system parameters without genipin included mean diameter of 312.20 ± 5.70 nm, PDI 0.342 ± 0.013 and zeta potential of 20.18 ± 2.28 mV. The genipin was introduced into the system analyzing different concentrations (0.5, 1.0 and 2.0 mM) and crosslinking times (3, 6, 12 and 24 h). Evaluating crosslinking time with genipin (0.5 mM) it was showed that varying the genipin reaction time the systems size ranged from 235.1 to 334.4 nm, the PDI from 0.321 to 0.392 and zeta potential 20.92 to 30.39 mV. The crosslinking degree that coud vary from 14 to 30 %. Nanoparticles without genipina, 6 h and 24 h crosslinking time were dried by spray-drying method. Analysis by scanning electron micrograph (SEM) revealed that the microparticles showed spherical morphology. The encapsulation rate was 75 ± 2.3 % using validated HPLC methodology. The infrared analysis showed chemical interactions between the components of the formulation. Thermal analysis showed that systems with a higher degree of crosslinking had a higher thermal stability. On release kinetics, increasing the degree of crosslinking was able to decrease the concentration and rate of release of triamcinolone. In studies with liver cancer cells (HepG2) and colon (HT-29), the microparticulate prepared with triamcinolone and 24 h of crosslinking with genipin showed a potential for antitumor activity in hepatic cell line HepG2. Therefore, a new delivery system for triamcinolone on polymeric nanoparticles of chitosan cocrosslinked with genipin and sodium sulfate was obtained with hepatic antitumor potential.

Síntese e caracterização de nanopartículas magnéticas de Co e Ni com aplicação em magneto hipertermia

Nanoparticles are importante for the study of new phenomena and for the development of new applications. Metallic magnetic nanoparticles like Cobalt and Nickel are important for their applications in nanoscience and nanotechnology. In this work, we report on the synthesis and characterization of Ni and Co nanoparticles. The nanoparticles were prepared by the modi- ed sol-gel method and were formed in the pore-network of the biopolymer quitosan. The reduction occurred in absence of H2 ux. The metallic particles and their monoxides have a face-centered- cubic structure. The metallic particles sizes ranged from 59 to 77 nm and from 19 to 50 nm for Ni and Co, respectively. Their monoxides chemically passivated the metallic cores, and after several weeks we have not observed further increase in oxidation. The synthesis method was tuned to obtain mainly the ferromagnetic phase. The system behaves like a core/shell structure with a ferromagnetic core and an antiferromagnetic shell. Exchange bias e ect was observed at temperatures below the Néel temperature. Both systems were submitted to an alternated magnetic eld and the heat released by the particles increased the temperature to 140°C in an interval of 5 min. Similar studies in samples dispersed in water increased the temperatures to 40-59°C, these results suggest that these materials are candidates for magnetic hyperthermia.

Nanopartículas catiônicas de poli (ácido lático) para liberação modificada de peptídios da peçonha do escorpião Tityus serrulatus

Reported accidents involving the poisoning scorpions are still frequent in Brazil, mainly caused by Tityus serrulatus, known as yellow scorpion. Although antivenom sera are produced routinely by various government laboratories, the effectiveness of its use depends on how quickly treatment is initiated and efficiency in the production of antibodies by the immunized animals. In this study, the development of cationic polymeric nanoparticles of poly(lactic acid) aimed to create a modified delivery system for peptides and proteins of T. serrulatus venom, able to enhance the production of serum antibodies against the scorpion toxins. The cationic nanoparticles were obtained by a low energy nanoprecipitation, after study of the parameters’ variations effects over the physicochemical properties of the particles. The surface functionalization of the nanoparticles with the hyperbranched polyethyleneimine was proved by zeta potential analysis and enabled the adsorption by electrostatic interaction of different types of proteins. The protein loading efficiency of 40-80 % to bovine serum albumin (BSA) and 100 % to scorpion venom peptides evaluated by spectrophotometry and polyacrylamide gel electrophoresis confirmed the success of the selected parameters established for obtainment of nanoparticles, produced with size between 100 to 250 nm. The atomic force microscopy analysis and in vitro release showed that the spherical nanoparticles provided a sustained release profile of proteins by diffusion mechanism, demonstrating the potential for application of the nanoparticles in vivo.

Nanopartículas catiônicas de poli (ácido lático) para liberação modificada de peptídios da peçonha do escorpião Tityus serrulatus

Reported accidents involving the poisoning scorpions are still frequent in Brazil, mainly caused by Tityus serrulatus, known as yellow scorpion. Although antivenom sera are produced routinely by various government laboratories, the effectiveness of its use depends on how quickly treatment is initiated and efficiency in the production of antibodies by the immunized animals. In this study, the development of cationic polymeric nanoparticles of poly(lactic acid) aimed to create a modified delivery system for peptides and proteins of T. serrulatus venom, able to enhance the production of serum antibodies against the scorpion toxins. The cationic nanoparticles were obtained by a low energy nanoprecipitation, after study of the parameters’ variations effects over the physicochemical properties of the particles. The surface functionalization of the nanoparticles with the hyperbranched polyethyleneimine was proved by zeta potential analysis and enabled the adsorption by electrostatic interaction of different types of proteins. The protein loading efficiency of 40-80 % to bovine serum albumin (BSA) and 100 % to scorpion venom peptides evaluated by spectrophotometry and polyacrylamide gel electrophoresis confirmed the success of the selected parameters established for obtainment of nanoparticles, produced with size between 100 to 250 nm. The atomic force microscopy analysis and in vitro release showed that the spherical nanoparticles provided a sustained release profile of proteins by diffusion mechanism, demonstrating the potential for application of the nanoparticles in vivo.

Análise tribo-termodinâmica da aplicação de nanopartículas de Al2O3 como aditivo lubrificante em compressor hermético de refrigeração

The thermodynamic performance of a refrigeration system can be improved by reducing the compression work by a particular technique for a specific heat removal rate. This study examines the effect of small concentrations of Al2O3 (50 nm) nanoparticles dispersion in the mineral oil based lubricant on the: viscosity, thermal conductivity, and lubrication characteristics as well as the overall performance (based on the Second Law of Thermodynamics) of the refrigerating system using R134a or R600a as refrigerants. The study looked at the influences of variables: i) refrigerant charge (100, 110, 120 and 130 g), ii) rotational speed of the condenser blower (800 and 1100 RPM) and iii) nanoparticle concentration (0.1 and 0.5 g/l) on the system performance based on the Taguchi method in a matrix of L8 trials with the criterion "small irreversibility is better”. They were carried pulldown and cycling tests according to NBR 12866 and NBR 12869, respectively, to evaluate the operational parameters: on-time ratio, cycles per hour, suction and discharge pressures, oil sump temperature, evaporation and condensation temperatures, energy consumption at the set-point, total energy consumption and compressor power. In order to evaluate the nanolubricant characteristics, accelerated tests were performed in a HFRR bench. In each 60 minutes test with nanolubricants at a certain concentration (0, 0.1 and 0.5 g/l), with three replications, the sphere (diameter 6.00 ± 0.05 mm, Ra 0.05 ± 0.005 um, AISI 52100 steel, E = 210 GPa, HRC 62 ± 4) sliding on a flat plate (cast iron FC200, Ra <0.5 ± 0.005 um) in a reciprocating motion with amplitude of 1 mm, frequency 20 Hz and a normal load of 1,96 N. The friction coefficient signals were recorded by sensors coupled to the HFRR system. There was a trend commented bit in the literature: a nanolubricant viscosity reduction at the low nanoparticles concentrations. It was found the dominant trend in the literature: increased thermal conductivity with increasing nanoparticles mass fraction in the base fluid. Another fact observed is the significant thermal conductivity growth of nanolubricant with increasing temperature. The condenser fan rotational speed is the most influential parameter (46.192%) in the refrigerator performance, followed by R600a charge (38.606%). The Al2O3 nanoparticles concentration in the lubricant plays a minor influence on system performance, with 12.44%. The results of power consumption indicates that the nanoparticles addition in the lubricant (0.1 g/L), together with R600a, the refrigerator consumption is reduced of 22% with respect to R134a and POE lubricant. Only the Al2O3 nanoparticles addition in the lubricant results in a consumption reduction of about 5%.

Análise tribo-termodinâmica da aplicação de nanopartículas de Al2O3 como aditivo lubrificante em compressor hermético de refrigeração

The thermodynamic performance of a refrigeration system can be improved by reducing the compression work by a particular technique for a specific heat removal rate. This study examines the effect of small concentrations of Al2O3 (50 nm) nanoparticles dispersion in the mineral oil based lubricant on the: viscosity, thermal conductivity, and lubrication characteristics as well as the overall performance (based on the Second Law of Thermodynamics) of the refrigerating system using R134a or R600a as refrigerants. The study looked at the influences of variables: i) refrigerant charge (100, 110, 120 and 130 g), ii) rotational speed of the condenser blower (800 and 1100 RPM) and iii) nanoparticle concentration (0.1 and 0.5 g/l) on the system performance based on the Taguchi method in a matrix of L8 trials with the criterion "small irreversibility is better”. They were carried pulldown and cycling tests according to NBR 12866 and NBR 12869, respectively, to evaluate the operational parameters: on-time ratio, cycles per hour, suction and discharge pressures, oil sump temperature, evaporation and condensation temperatures, energy consumption at the set-point, total energy consumption and compressor power. In order to evaluate the nanolubricant characteristics, accelerated tests were performed in a HFRR bench. In each 60 minutes test with nanolubricants at a certain concentration (0, 0.1 and 0.5 g/l), with three replications, the sphere (diameter 6.00 ± 0.05 mm, Ra 0.05 ± 0.005 um, AISI 52100 steel, E = 210 GPa, HRC 62 ± 4) sliding on a flat plate (cast iron FC200, Ra <0.5 ± 0.005 um) in a reciprocating motion with amplitude of 1 mm, frequency 20 Hz and a normal load of 1,96 N. The friction coefficient signals were recorded by sensors coupled to the HFRR system. There was a trend commented bit in the literature: a nanolubricant viscosity reduction at the low nanoparticles concentrations. It was found the dominant trend in the literature: increased thermal conductivity with increasing nanoparticles mass fraction in the base fluid. Another fact observed is the significant thermal conductivity growth of nanolubricant with increasing temperature. The condenser fan rotational speed is the most influential parameter (46.192%) in the refrigerator performance, followed by R600a charge (38.606%). The Al2O3 nanoparticles concentration in the lubricant plays a minor influence on system performance, with 12.44%. The results of power consumption indicates that the nanoparticles addition in the lubricant (0.1 g/L), together with R600a, the refrigerator consumption is reduced of 22% with respect to R134a and POE lubricant. Only the Al2O3 nanoparticles addition in the lubricant results in a consumption reduction of about 5%.

Influência da interação dipolar nas fases magnéticas de nanopartículas esféricas com estrutura núcleo@camada

Bi-magnetic core@shell nanoparticle has attracted attention several researchers because great applicability that they offer. The possibility of combining different functionalities of magnetic materials make them a key piece in many areas as in data processing permanent magnets and biomagnetics sistems. These nanoparticles are controlled by intrinsic properties of the core and shell materials as well as the interactions between them, besides size and geometry effects. Thus, it was developed in this thesis a theoretical study about dipolar interaction contribution between materials different magnetic properties in bi-magnetic core@shell nanoparticles conventional spherical geometry. The materials were analyzed CoFe2O4, MnFe2O4 e CoFe2 in various combinations and sizes. The results show that the impact of the core dipole field in the shell cause reverse magnetization early its, before of the core, in nanoparticle of CoFe2O4(22nm)@CoFe2(2nm), thereby causing a decrease coercivity field of 65% in comparection with simple nanoparticle of CoFe2O4 (HC=13.6 KOe) of same diameter. The large core anisotropy in conventional nanoparticle makes it the a stable dipolar field source in the shell, that varies length scale of the order of the core radius. Furthermore, the impact of dipolar field is greatly enhanced by the geometrical constraints and by magnetics properties of both core@shell materials. In systems with core coated with a thin shell of thickness less than the exchange length, the interaction interface can hold reversal the shell occurring an uniform magnetization reversal, however this effect only is relevant on systems where the dipole field effects is weak compared with the exchange interaction.