>Magister Scientiae - MSc / During the course of this study iron oxide nanoparticles, which have been researched for drug-targeted delivery, were synthesised via the co-precipitation method and characterised using various methods. This study focused on the role of relevant capping agents for the inhibition of agglomeration of the particles; chitosan, polyvinyl alcohol (PVA) and poly lactic glycolic acid (PLGA) were the capping agents of interest. The study is an assessment of the effects brought about the different capping agents used for this work. The prepared particles were then capped with the different capping agents followed by the loading of the drug curcumin. Various analytical methods were used to analyse the particles such as High resolution transmission electron microscopy (HR-TEM), Superconducting quantum interference device (SQUID), Fourier Transform Infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Thermogravimetric analysis (TGA) and zeta potential. PVA, chitosan and PLGA capped SPIONS were successfully prepared and verified by FT-IR spectrometry, various sizes were prepared almost ranging the same for the successfully prepared particles verified by XRD. The resultant particles were found to be spherical with an average particles size between 13- 22 nm. From the study it was concluded that the addition of the different capping agents resulted in the reduction of the intensity of the peaks in XRD, it was also found out the presence of the capping agents did not alter the crystalline phase of the particles. From the study it was also observed that higher saturation magnetization was experienced where PVA was used as the capping agents.

Materials on the nanoscale have very interesting properties. Hence, they are commonly used for a variety of applications such as drug delivery, bio-imaging and sensing devices. Moreover, coating these particles with other materials forming core@shell or Janus particles can further enhance their properties. However, for the particles to be used in medical and electronic devices, their properties such as size, shape and composition need to be precisely controlled. In this PhD., an emulsification technique was chosen to investigate the synthesis of nanoparticles; it is a simple process, does not require any harsh chemicals or temperature and is fast. Emulsification occurs when two or more immiscible liquids and surfactants are mixed. Here, emulsion droplets were produced using a microfluidic device which allowed for the creation of uniform droplets. These were employed as templates to synthesise and assemble nanomaterials. The main aim of the Ph.D. was to develop a droplet based synthesis process to generate nanoparticles and then assemble them into core@shell particles. This Ph.D., starts by synthesising Fe3O4 nanoparticles (~ 12 nm) and assembling them into microparticles (~ 1µm 2µm) using emulsion droplets as microreactors. By tuning the surfactant, droplet size and evaporation rate of the dispersed phase, microparticles of varying shapes and sizes, such as spherical or crumbled shapes, were produced. When these particles are compared with the commercially available particles, the magnetic content of the in-house particles, or sometimes referred to as Loughborough University Enterprises Ltd. (LUEL), are much higher and more uniform, hence resulting in faster separation when used for extraction of analytes. LUEL particles were supplied as part of commercial collaboration. The use of Pickering emulsions were then explored to create core@shell particles using gold nanoparticles instead of a surfactant to produce gold shells and the addition of pre-synthesised Fe3O4 nanoparticles results in Fe3O4@Au core@shell particles. This is the first time Pickering emulsions were used to produce Fe3O4@Au core@shell particles (~ 1.5 µm) within a microfluidic device. However, the shells were not uniform in thickness. In order to improve the coverage, nanoparticles were synthesised in situ at the droplet interface. By placing the gold chloride (AuCl4-) in the continuous phase and by varying the concentration of the electron donor in hexane droplet, single crystal gold nanoparticles and platelets were formed. The reaction is spontaneous at room temperature, creating gold nanoparticles at the interface of the emulsion droplet. The size and shape of the gold nanoparticles were controlled by varying the concentration of the reactants and the size of the droplets. By adding pre-synthesised particles (Fe3O4 nanoparticles) to the droplet, Au@Fe3O4 core@shell particles were formed with an approximate size of 250 nm. The same concept of forming core@shell particles using gold nanoparticles was further expanded by using other metal ions; palladium and silver. Unlike gold, palladium and silver only formed spherical nanoparticles, no platelets were observed. The addition of preformed iron oxide nanoparticles to the palladium results in core@shell particles. However, in the case of silver, no core@shell particles were formed. The study of the rate of reaction was conducted to understand the details of the mechanism. Overall, the process developed in this Ph.D. study allows for the facile synthesis of core@shell particles in a rapid, high throughput reaction. In the future, it is believed it could be scaled up for commercial purposes.

Zhou, Wenjia = 聚苯乙烯/銀聚合物納米棒陣列的合成、表征與生長的研究 / 周文佳. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 69-73). / Text in English; abstracts in English and Chinese. / Zhou, Wenjia = Ju ben yi xi / yin ju he wu na mi bang zhen lie de he cheng, biao zheng yu sheng zhang de yan jiu / Zhou Wenjia. / Chapter I. --- Abstract / Chapter IV. --- Acknowledgement / Chapter V. --- Contents / Chapter 1 --- Introduction / Chapter 1.1 --- Motivations / Chapter 1.2 --- Overview of the thesis / Chapter 2 --- Instruments / Chapter 2.1 --- Introduction to electron microscopes / Chapter 2.2 --- Scanning electron microscope / Chapter 2.2.1 --- Introduction to SEM working principle / Chapter 2.2.2 --- Electron specimen interactions and their applications in SEM / Chapter 2.2.3 --- Specific SEM conditions in the experiments / Chapter 2.3 --- Transmission electron microscope / Chapter 2.3.1 --- Introduction to TEM working principle / Chapter 2.3.2 --- Imaging mode and diffraction mode in TEM / Chapter 2.3.3 --- X-ray microanalysis with TEM / Chapter 2.3.4 --- Specific TEM conditions in the experiments / Chapter 3 --- Anodic aluminum oxide templates with different parameters / Chapter 3.1 --- Introduction to self-ordered anodic aluminum oxide / Chapter 3.1.1 --- Electrochemistry of anodic alumina / Chapter 3.1.2 --- Pore growth mechanism / Chapter 3.1.3 --- Self-ordered alumina by two-step anodization / Chapter 3.1.4 --- Other advanced methods for fabrication of monodomain AAO / Chapter 3.1.5 --- Applications of AAO templates in nanomaterials fabrication / Chapter 3.2 --- Preparation procedures of porous AAO templates we used / Chapter 3.2.1 --- Experimental setup / Chapter 3.2.2 --- General preparation procedures of AAO thin film on Al / Chapter 3.3 --- Experimental data of AAO templates with different parameters / Chapter 3.3.1 --- Different interpore distances / Chapter 3.3.2 --- Different pore depths and pore sizes / Chapter 3.3.3 --- Calibration of AAO templates pore depths and pore sizes at different anodic potentials / Chapter 4 --- Preparation of free standing polystyrene nanorods arrays with different parameters / Chapter 4.1 --- General preparation procedures of free standing polymer nanorods arrays / Chapter 4.2 --- Different rods intervals and diameters / Chapter 4.3 --- Limitations to the rods lengths control / Chapter 4.4 --- Discussion on the polymer properties for the successful preparation of free standing polymer rods arrays / Chapter 5 --- Thermal reduction method to embed Ag nanoparticles inside the polymer rods / Chapter 5.1 --- General preparation procedures of PS/Ag nanorods arrays / Chapter 5.2 --- Analysis method and procedure of Ag nanoparticles inside PS rods / Chapter 5.3 --- Typical TEM images of the three series samples / Chapter 5.4 --- Data analysis of Ag nanoparticles inside PS rods / Chapter 5.5 --- Discussion on Ag particles growth process / Chapter 5.6 --- Conclusion and suggestions for improvement / Chapter 6 --- Conclusion / Reference / Appendix

Fang, Qunling. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 168-170). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Um dispositivo eletroquímico foi desenvolvido para a determinação simultânea de sulfametoxazol (SMX) e trimetoprim (TMP), utilizando voltametria de pulso diferencial e um eletrodo de carbono vítreo (GC) modificado com o compósito óxido de grafeno reduzido (rGO) e nanopartículas de prata (AgNPs), sintetizados por dois métodos: químico e o eletroquímico. A morfologia e o comportamento eletroquímico dos eletrodos GC modificados com os compósitos rGO/AgNPs (método químico) e rGO-AgNPs (método eletroquímico) foram caracterizados por microscopia eletrônica de varredura acoplada a um canhão de elétrons (FEG-SEM) e voltametria cíclica (CV). Essas técnicas demostraram que, nos dois métodos utilizados, o óxido de grafeno (GO) foi modificado com as AgNPs, e que o compósito sintetizado pelo método eletroquímico apresentou uma melhor dispersão das nanopartículas, resultando em um aumento da área superficial quando comparado ao compósito rGO/AgNPs. Assim, o eletrodo GC/rGO-AgNPs foi avaliado e otimizado na determinação simultânea de SMX e TMP e atingiu limites de detecção de 0,6 µmol L-1 para o SMX e 0,4 µmol L-1 para o TMP. O dispositivo eletroquímico proposto, GC/rGO-AgNPs, foi aplicado com sucesso na determinação simultânea de SMX e TMP em águas residuárias. / An electrochemical device was developed for the simultaneous determination of sulfamethoxazole (SMX) and trimethoprim (TMP) using differential pulse voltammetry, and a glassy carbon electrode (GC) modified with the reduced graphene oxide composite (rGO) and silver nanoparticles (AgNPs), synthesized by two methods: chemical and electrochemical. The morphology and the electrochemical behavior of the GC electrode modified with composite rGO/AgNPs (chemical method) and rGO-AgNPs (electrochemical method) were characterized by scanning electron microscopy coupled to an electron gun (FEG-SEM) and cyclic voltammetry (CV). These techniques demonstrated that, in both methods, the graphene oxide (GO) was modified with AgNPs, and the composite synthesized by the electrochemical method showed a better dispersion of the nanoparticles, resulting in an increased surface area when compared to the composite rGO/ AgNPs. Thus, the GC/rGO-AgNPs electrode was evaluated and optimized for simultaneous determination of SMX and TMP and achieved detection limits of 0,6 µmol L-1 to SMX and 0,4 µmol L-1 for the TMP. The proposed electrochemical device, GC/rGO-AgNPS, was successfully applied for the simultaneous determination of SMX and TMP in wastewater.

Este trabalho de mestrado descreve a avaliação do emprego do TiO2, obtido por diferentes rotas de sínteses e do TiO2 P25 ambos modificados superficialmente com prata e cobre, como catalisador no processo de fotocátalise heterogênea visando a degradação de fenol e efluentes industriais, especificamente efluentes fenólicos. A deterioração dos recursos hídricos é uma das maiores preocupações da sociedade moderna. Dentre os principais responsáveis pela diminuição sistemática na qualidade dos sistemas aquáticos, destacam-se os compostos orgânicos poluentes presentes em efluentes industriais. Dentre esta vasta gama de compostos, os fenóis mostram-se especialmente deletérios ao meio ambiente, devido a sua elevada toxicidade, tendência a bioacumulação e grandes quantidades em que são gerados pelos mais diversos tipos de atividades produtivas. Este trabalho avaliou a aplicação do TiO2 sintetizado pelos métodos de sol-gel e precipitação homogênea na degradação de fenol e no tratamento de efluentes industriais fenólicos. De um modo geral, após 90 minutos de tratamento estes materiais permitiram uma redução de 90% no teor de fenol e de 30% na concentração de carbono orgânico total. Estes resultados são superiores aos obtidos empregando-se TiO¬2 P25 (material comercial mais utilizado neste tipo de processo). A aplicação destes materiais sintetizados na remediação de uma matriz real complexa (efluente industrial) também mostrou uma melhoria na redução de fenol (cerca de 16%) em comparação ao catalisador comercial. Além da síntese do TiO2, também avaliou-se a modificação da superfície das partículas deste semicondutor com prata e cobre visando mais uma vez um aumento na eficiência do processo de fotodegradação. A deposição de prata ou cobre nas partículas do TiO2 P25 promoveu um aumento na capacidade de redução média de fenol e carbono orgânico deste poluente de 15 e 45%, respectivamente. A modificação superficial do TiO2 sintetizado tanto por sol-gel quanto por precipitação homogênea gerou um aumento médio na eficiência catalítica do semicondutor de 30% na mineralização de fenol e 98% na redução da concentração inicial desta espécie. Aplicando estes catalisadores modificados no tratamento do efluente fenólico houve um aumento na mineralização de 32% e uma redução na concentração inicial de fenol de 98% do efluente fenólico. De maneira geral a síntese do TiO2 e a modificação superficial das partículas do catalisador com prata e cobre mostraram-se bastante promissoras para uma futura aplicação destes materiais na remediação de efluentes fenólicos. / This work describes the evaluation of TiO2, obtained from different synthesis routs and superficially modified with silver and copper, as the catalyst in the heterogeneous photocatalysis process to promote phenol degradation and industrial effluents remediation, specifically phenolic effluents. The deterioration of water resources is one the greatest concerns of modern society. Among many responsible for the systematic decreases in the aquatic systems quality, special attention has been give to the organic pollutant compounds presents in the industrial effluents. Among this wide range compounds, the phenols have been showed many deleterious effect to the environment, especially because their high toxicity, bioaccumulation tendency and large generation by several types of productive activities. This work evaluated the application of TiO2, synthesized by sol-gel and precipitation methods, for phenol degradation and phenolic industrial effluent treatment. In general, after 90 minutes of treatment, these materials allowed to rich a reduction of 90% in the phenol content and of 30% in the total organic carbon concentration. These results were superior those obtained using TiO2 P25 (commercial material usually employed in this kind of treatment). The application of these synthesized materials in the remediation of a real complex matrix (industrial effluent) also showed an improvement in the phenol reduction (about 16%) in comparison with the commercial catalysis. Besides the TiO2 synthesis, the semiconductor surface modification with silver and copper was also evaluated aiming to increase the photodegradation process efficiency. The silver and copper deposition on TiO2 P25 particles promoted an increase of 15 and 45% in average capacity of phenol and organic carbon reduction, respectively. The superficial modification of TiO2 synthesized either for sol-gel or precipitation allowed an average improvement in the catalytic efficiency of 30% for phenol mineralization and 98% to phenol concentration reduction. It was observed an increase of 32% in the mineralization and of 98% in the phenol content reduction applying these modified catalysis in the treatment of a phenolic effluent. In general, the synthesis of TiO2 and its superficial modification with silver and copper have showed a promising alternative to allow a future application of these catalysts in the phenolic effluents remediation.

A convergência entre a biotecnologia e a nanotecnologia tem levado ao desenvolvimento de novos nanobiocompósitos híbridos com funções sinérgicas que incorporam as propriedades de reconhecimento dos biomateriais com as propriedades eletrônicas, ópticas e catalíticas únicas das nanopartículas. Apesar do recente desenvolvimento na síntese de nanobiocompósitos, a aplicação biomédica destes materiais ainda apresenta muitos desafios, já que não apenas uma conjugação apropriada é requerida, mas também outros importantes aspectos relacionados à biocompatibilidade. O presente trabalho tem como objetivo expandir o campo da síntese e caracterização de nanoparticulas funcionalizadas com biomoléculas. Em especial, visamos o entendimento e caracterização das interações entre nanopartículas de ouro (AuNPs) e proteínas, por meio do estudo de dois sistemas distintos: AuNPs funcionalizadas com Jacalina, e AuNPs funcionalizadas com a proteína BeCen1. No primeiro sistema, o interesse advém da capacidade da lectina Jacalina de reconhecer o dissacarídeo (Galβ1-3GalNAc) associado a tumores. Neste caso, AuNPs formadas na presença do dendrímero poli(amidoamina) geração 4.0 (PAMAM G4) foram conjugadas com a Jacalina marcada com o fluóroforo Isotiocianato de fluoresceína (FITC). A formação do complexo AuNP-PAMAM G4/Jacalina foi confirmada por Microscopia Eletrônica de Transmissão (TEM), Espalhamento de Luz Dinâmico (DLS), Espectroscopia de Absorção no UV-VIS e vibracional (FTIR). A interação entre as AuNP-PAMAM G4 e a Jacalina parece ser um processo dirigido por entropia com afinidade moderada e formação de complexo, segundo os resultados de Calorimetria de Titulação Isotérmica (ITC) e supressão da fluorescência. Os resultados de Dicroísmo Circular (CD) mostraram que a conjugação da Jacalina com as AuNP-PAMAM G4 não alterou sua estrutura secundária. Testes realizados em cultura de células revelaram que o complexo apresenta maior afinidade e citotoxicidade pelas células de carcinoma do colo de útero humano (HeLa) se comparadas com fibroblastos saudáveis de adipócitos de camundongo (L929). Estes resultados são relevantes uma vez que demonstram o potencial do complexo AuNP-PAMAM G4/Jacalina-FTIR para aplicações biomédicas incluindo diagnóstico e tratamento de câncer. O segundo sistema é interessante devido a habilidade da proteína BeCen1 em formar filamentos nanométricos em função da temperatura. As AuNPs foram formadas na presença da proteína utilizando ácido fórmico diluído como agente redutor e o excesso de proteína foi separado por Cromatografia de Exclusão Molecular. Análises de CD revelaram uma pequena diminuição no conteúdo de α-hélices, confirmado por FTIR, o que pode estar relacionado à interação das AuNPs com os grupamentos amida desta proteína. Medidas de espalhamento de luz revelaram um aumento da turbidez da suspensão do complexo AuNP-BeCen1 com o aumento da temperatura e imagens de TEM, com e sem aquecimento, confirmaram uma mudança de padrão no arranjo das AuNPs. Estes resultados revelam a possibilidade de fabricação de nanobiocompósitos termorresponsivos, o que pode ser muito importante para aplicações em nanodispositivos. / The convergence between biotechnology and nanotechnology has led to the development of new hybrid nanocomposites that conjugate the bio-recognization properties of biomaterials and the unique electronic, optic and catalytic properties of the nanoparticles. Despite the recent advances in the development of nanobiocomposites, the biomedical applications of these materials are still limited, among other factors, by the low efficiency of functionalization and biocompatibility. The present study was aimed at developing proteinconjugated nanoparticles for application in nanomedicine. Our main focus were the understanding and characterization of the interactions between proteins and gold nanoparticles (AuNPs), which was accomplished using two distinct systems, viz.: Jacalin-functionalized AuNPs, and Becen1-functionalized AuNPs. In the former, the interest is due the capability of the protein Jacalin of recognize the disaccharide (Galβ1-3GalNAc), largely expressed in some tumors cells. AuNPs were synthesized in the presence of the polyamido amine generation 4.0 (PAMAM G4) and conjugated with a Jacalin target with the fluorescein isothiocyanate (FITC). The excess of protein was removed by centrifugation and the complex formation was confirmed by Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), UV-VIS Absorption and Vibrational Spectroscopy (FTIR). The interactions between AuNP-PAMAM G4 and Jacalin seemed to be driven by an entropic process with moderate affinity and complex formation, as revealed by Isothermal Titration Calorimetry (ITC) and quenching fluorescence measurements. Furthermore, Circular Dichroism (CD) analyses revealed that protein maintained its secondary structure upon conjugation with the nanoparticles. In vitro tests revealed that the AuNPs/Jacalin complexes presented higher affinity and cytotoxicity against human cervical cancer cell (HeLa) compared to healthy mouse fibroblasts (L929). These results are relevant, since the AuNP-PAMAM G4/Jacalin-FITC complex may be used for biomedical applications including cancer treatment and diagnostics. The second nanocomplex, comprising AuNPs and BeCen1, was chosen due to the ability of BeCen 1 to polymerize in the form of nanometric filaments as a function of temperature. The AuNPs were formed in the presence of the protein using diluted formic acid as reducing agent and the excess of protein was removed by Molecular Exclusion Chromatography. CD analysis showed a decrease in the -helix structures confirmed by FTIR, which may be related to the interaction between the AuNPs and the amide groups of the protein. Light scattering measurements revealed an increase in the turbidity of the dispersions upon increasing the temperature, indicating a change in the arrangement of the AuNPs. Such BeCen-1 induced alignment was confirmed by TEM images. The latter results point to the possibility of fabrication of novel thermoresponsive nanobiocomposites, which are of great relevance for nanodevices applications.

Aterosclerose é uma doença inflamatória e proliferativa que tem início quando fatores de risco alteram o endotélio vascular. Células inflamatórias e vasculares liberam citocinas e fatores de crescimento que estimulam a proliferação e migração das células de músculo liso e a síntese de componentes da matriz extracelular. A nanoemulsão lipídica LDE se concentra em regiões onde a proliferação celular e a inflamação são maiores, tornando-se um veículo para fármacos. O etoposide, fármaco antiproliferativo, ainda não foi explorado no tratamento da aterosclerose. O paclitaxel recobre stents utilizados em angioplastia para evitar a reestenose. A associação do LDE-etoposide ao LDE-paclitaxel aumentaria o efeito antiproliferativo dos fármacos isolados, por agirem em diferentes fases do ciclo celular. Este estudo tem por objetivos avaliar a eficácia do tratamento com LDE-etoposide e com a combinação LDE-etoposide/LDE-paclitaxel da aterosclerose induzida por dieta rica em colesterol em coelhos; comparar a eficácia dos tratamentos; no grupo de tratamento mais eficaz e no grupo Controle, avalia a expressão protéica de receptores de lipoproteínas, citocinas, MMP9 e marcadores de proliferação celular. Para tanto, 27 coelhos receberam dieta rica em colesterol por 8 semanas. Depois de 4 semanas, foram divididos em 3 grupos: grupo Controle, que recebeu 6 mL de solução salina intravenosa; LDE-etoposide, que recebeu dose de 6mg/kg; e grupo Combinação, que recebeu LDE-etoposide/LDE-paclitaxel nas doses de 6mg/kg e 4mg/kg, respectivamente. Os tratamentos foram administrados uma vez por semana durante 4 semanas. Foram avaliados perfil lipídico, hematológico, ponderal e o consumo de ração. Após a eutanásia, as lesões ateroscleróticas macroscópicas foram medidas. Depois, o arco aórtico foi analisado por morfometria e por imunohistoquímica. Foi observado que não houve diferença no perfil ponderal e no consumo de ração entre os grupos de estudo. No perfil lipídico, ao final do estudo, as concentrações de colesterol total e de triglicérides aumentaram em todos os grupos. O perfil hematológico mostrou redução do número de hemácias nos grupos de tratamento ao final do estudo. Em comparação com o grupo Controle, os animais tratados com LDE-etoposide apresentaram lesões ateroscleróticas 11 vezes menores e o grupo Combinação, apresentou lesões 3 vezes menores. Na análise morfométrica, a área total e a espessura da aorta foram menores no grupo LDE-etoposide quando comparado com os outros dois grupos. O grupo tratado com LDE-etoposide apresentou presença de macrófagos e de células de músculo liso menor que os grupos Controle e Combinação. Como o tratamento com LDE-etoposide apresentou uma maior eficácia, a avaliação dos outros fatores foi feita apenas neste grupo e no grupo Controle para comparação. O grupo LDE-etoposide apresentou menor expressão protéica dos receptores de lipoproteínas, das citocinas inflamatórias, da MMP9 e dos marcadores de proliferação celular topoisomerase II e tubulina. As avaliações mostraram que o tratamento com LDE-etoposide foi mais eficaz no tratamento das lesões ateroscleróticas induzidas em coelhos do que a combinação entre LDE-etoposide/LDE-paclitaxel / Atherosclerosis is an inflammatory and proliferative disease that is triggered by risk factors damaging vascular endothelium. Inflammatory and vascular cells release cytokines and growth factors, promoting the proliferation and migration of smooth muscle cells and extracellular matrix elements synthesis. LDE, an artificial nanoemulsion, concentrates in areas of greater proliferation and inflammation rates and can be used as a vehicle to direct drugs to those cells. Etoposide, an antiproliferative drug, have not been studied in atherosclerosis treatment. Paclitaxel is used in drug-eluting stents to avoid restenosis. The association of LDE-etoposide and LDE-paclitaxel would enhance the antiproliferativo effect of the isolated drugs, due to act in different cell cycle phase. The aim of this study was to evaluate the effectiveness of the treatment with LDE-etoposide and with LDE-etoposide/LDE-paclitaxel of atherosclerosis induced by a cholesterol-rich diet in rabbits; compare the effectiveness of these treatments; in the most effective treatment group and in Control group, evaluate the protein expression of lipoprotein receptors, cytokines, MMP9 and cell proliferation markers. To do so, 3 groups of 9 rabbits were fed a cholesterol-rich diet during 8 weeks then the animals were separated in 3 groups: Control, intravenously injected with 6mL of saline solution; LDE-etoposide, injected with a dose 6mg/kg; and Combination, injected with LDE-etoposide/LDE-paclitaxel in a dose of 6mg/kg and 4mg/kg, respectively. Treatments were administered once a week during 4 weeks. Lipids, blood cell count, weight and food intake were evaluated. The animals were sacrificed and the macroscopic atherosclerotic lesions were measured. Later, the aortic arch was analyzed by microscopic morphometry and by immunohistochemistry. It was seen that there was no difference in food intake and weight between study groups. Total cholesterol and triglycerides concentration increased in all groups. Blood cell count showed reduction of red blood cell in treatment groups at the end of the study. Animals treated with LDE-etoposide showed 11-fold less lesions and Combination group showed 3-fold less lesions than Control group. By morphometric analysis, total area and thickness of aorta were smaller in LDE-etoposide group than the other groups. LDE-etoposide group showed less macrophages and smooth muscle cells than Control and Combination groups. As treatment with LDE-etoposide showed a better efficacy, evaluation of other factor were performed only in LDE-etoposide and Control group, to perform a comparison. LDE-etoposide showed less protein expression of lipoprotein receptors, cytokines, MMP9, and of cell proliferation markers topoisomerase II and tubulina. The analysis showed that LDE-etoposide treatment was more effective in treating atherosclerotic-induced lesions in rabbits than the combination between LDE-etoposide/LDE-paclitaxel

The objective of this research was the development of an efficient method for the preparation of silver-polymer nanocomposites containing finely dispersed silver nanoparticles. The surface of nanosilver was functionalized by thiolation with 2-aminoethanethiol. Amino-modified nanosilver was covalently bonded to polyacrylic acid, biodegradable polymers like acid terminated polylactic acid, ester terminated poly(DL-lactide-co-glycolide) and acid terminated poly(DL lactide-co-glycolide) in the presence of diisopropylcarbodiimide by carbodiimide method. Esterification of the carboxyl groups of Ag-polyacrylic acid by hydrochloric acid in methanol resulted in the formation of a stable colloidal dispersion of Ag nanoparticles in the polymer matrix. It was observed that not just acid terminated polymers but also ester terminated polymers could react with functionalized nanosilver. This unusual reaction was due to the aminolysis of the ester bond in the polymer chain by the surface amino groups. Silver-polymer nanocomposites obtained with acid terminated polylactic acid and poly(DL-lactide-co-glycolide) contained highly dispersed nanosilver in the polymer matrix in comparison with the ester terminated poly(DL-lactide-co-glycolide). Chemical and structural characteristics of the obtained materials were studied by instrumental methods. Attained biodegradable materials confirmed X-ray contrast and bactericidal properties, which could be eventually used for biomedical applications.

No description available.