Rozprawy doktorskie na temat „Cellular Delivery - Anionic Nanoparticles”

Cancer remains one of the world’s most devastating diseases, with more than 10 million new cases every year. However, traditional treatments have proven insufficient for successful medical management of cancer due to the chemotherapeutics’ difficulty in achieving therapeutic concentrations at the target site, non-specific cytotoxicity to normal tissues, and limited systemic circulation lifetime. Although, a concerted effort has been placed in developing and successfully employing nanoparticle(NP)-based drug delivery vehicles successfully mitigate the physiochemical and pharmacological limitations of chemotherapeutics, work towards controlling the subcellular fate of the carrier, and ultimately its payload, has been limited. Because efficient therapeutic action requires drug delivery to specific organelles, the subcellular barrier remains critical obstacle to maximize the full potential of NP-based delivery vehicles. The aim of my dissertation work is to better understand how NP-delivery vehicles’ structural, chemical, and physical properties affect the internalization method and subcellular localization of the nanocarrier. In this work we explored how side-chain and backbone modifications affect the conjugated polymer nanoparticle (CPN) toxicity and subcellular localization. We discovered how subtle chemical modifications had profound consequences on the polymer’s accumulation inside the cell and cellular retention. We also examined how complexation of CPN with polysaccharides affects uptake efficiency and subcellular localization. This work also presents how changes to CPN backbone biodegradability can significantly affect the subcellular localization of the material. A series of triphenyl phosphonium-containing CPNs were synthesized and the effect of backbone modifications have on the cellular toxicity and intracellular fate of the material. A mitochondrial-specific polymer exhibiting time-dependent release is reported. Finally, we present a novel polymerization technique which allows for the controlled incorporation of electron-accepting benzothiadiazole units onto the polymer chain. This facilitates tuning CPN emission towards red emission. The work presented here, specifically, the effect that side-chain and structure, polysaccharide formulation and CPN degradability have on material’s uptake behavior, can help maximize the full potential of NP-based delivery vehicles for improved chemotherapeutic drug delivery.

Mesoporous silica nanoparticles (MSNPs) possess large surface areas and ample pore space that can be readily modified with specific functional groups for targeted binding of bioactive materials to be transported through cellular barriers. Engineered silica nanoparticles (ESNP) have been used extensively to deliver bio-active materials to target intracellular sites, including as non-viral vectors for nucleic acid (DNA/RNA) delivery such as for siRNA induced interference. The reverse process guided by the same principles is called “nanoharvesting”, where valuable biomolecules are carried out and separated from living and functioning organisms using nano-carriers. This dissertation focuses on ESNP design principles for both applications. To investigate the bioactive materials loading, the adsorption of antioxidant flavonoids was investigated on titania (TiO2) functionalized MSNPs (mean particle diameter ~170 nm). The amount of flavonoid adsorbed onto particle surface was a strong function of active group (TiO2) grafting and a 100-fold increase in the adsorption capacity was observed relative to nonporous particles with similar TiO2 coverage. Active flavonoid was released from the particle surface using citric acid-mediated ligand displacement. Afterwards, nanoharvesting of flavonoids from plant hairy roots is demonstrated using ESNP in which TiO2 and amine functional groups are used as specific binding sites and positive surface charge source, respectively. Isolation of therapeutics was confirmed by increased pharmacological activity of the particles. After nanoharvesting, roots are found to be viable and capable of therapeutic re-synthesis. In order to identify the underlying nanoparticle uptake mechanism, TiO2 content of the plant roots was quantified with exposure to nanoparticles. Temperature (4 or 23 °C) dependent particle recovery, in which time dependent release of ESNP from plant cells showed a similar trend, indicated an energy independent process (passive transport). To achieve the selective separation and nanoharvesting of higher value therapeutics, amine functionalized MSNPs were conjugated with specific functional oligopeptides using a hetero-bifunctional linker. Fluorescence spectroscopy was used to confirm and determine binding efficiency using fluorescently attached peptides. Binding of targeted compounds was confirmed by solution depletion using liquid chromatography–mass spectrometry. The conjugation strategy is generalizable and applicable to harvest the pharmaceuticals produced in plants by selecting a specific oligopeptide that mimic the appropriate binding sites. For related gene delivery applications, the thermodynamic interaction of amine functionalized MSNPs with double-stranded (ds) RNA was investigated by isothermal titration calorimetry (ITC). The heat of interaction was significantly different for particles with larger pore size (3.2 and 7.6 nm) compared to that of small pore particles (1.6 nm) and nonporous particles. Interaction of dsRNA also depended on molecular length, as longer RNA (282 base pair) was unable to load into 1.6 nm particles, consistent with previous confocal microscopy observations. Calculated thermodynamic parameters (enthalpy, entropy and free energy of interaction) are essential to design pore size dependent dsRNA loading, protection and delivery using MSNP carriers. While seemingly diverse, the highly tunable nature of ESNP and their interactions with cells are broadly applicable, and enable facile nano-harvesting and delivery based on a continuous uptake-expulsion mechanism.

An outstanding challenge in modern medicine is the safe and efficient delivery of drugs. One approach to improve drug delivery yield and increase specificity towards diseased cells, is to employ a drug carrier to facilitate transport. Promising steps towards developing such a carrier have been taken by the nascent field of nanomedicine: nanometer-sized particles designed to evade premature excretion, non-specific absorption, and the body’s immune response, can reduce undesired drug loss, while also increasing specific drug uptake into diseased cells through targeting surface modifications. However, progress is limited by incomplete knowledge of the ‘ideal’ nanoparticle design as well as a lack of appropriate high resolution construction methods for its implementation. DNA origami, a modular, nanometer-precise assembly method that would enable the rapid testing of particle properties as well as massively parallel fabrication, could provide an avenue to address these needs. In this thesis, I employed the DNA origami method to investigate how nanoscale shape and ligand functionalization affect nanoparticle uptake into cultured endothelial cells. In the first part, I evaluated the uptake yield of a series of eight shapes that ranged from 7.5 nm to 400 nm in their individual dimensions. The best performing shape of that study, a 15 × 100 nm DNA origami nanocylinder, was internalized 18-fold better than a dsDNA control of the same molecular weight. In a follow up study, I decorated this nanocylinder with integrin-targeting cyclic RGD peptides. This surface functionalization increased cellular uptake another 13-fold. In addition, uptake yield and the ratio of internalized versus surface-bound particles depended on the number of ligands present on the nanoparticle surface. This work represents a significant first step towards attaining the ability to design and implement an 'ideal' nanoparticle drug carrier. In the future, the DNA origami method can be used as a platform technology to further expand our understanding of transport properties of drug carriers and achieve safer and more efficient drug delivery.

Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2006.<br>Dr. X. Hu, Committee Member ; Dr. Al Merrill, Committee Member ; Dr. Niren Murthy, Committee Member ; Dr. Gang Bao, Committee Chair ; Dr. Nicholas Hud, Committee Member. Includes bibliographical references.

Cisplatin and its analogues are important drugs for the treatment of many malignant tumors, but many side effects and deactivation processes may occur. In order to overcome these limits, the Pt(IV) complexes higher inertness can be exploited. They are activated to their corresponding Pt(II) active metabolite only in the tumor site, taking advantage of the hypoxic and reducing milieu of neoplastic cells: for this reason, they are considered prodrugs. Furthermore, passive Drug Targeting and Delivery (DTD) strategies can be developed to improve the selective accumulation of such species. The tumor tissue increased vascular permeability, due to an irregular architecture of the blood vessels, and the reduced drainage of the lymphatic system allow macromolecules of suitable dimensions (e.g. nanoparticles (NPs), liposomes, etc.) to extravasate and to be retained for longer time. Therefore, nanosized carriers decorated with anticancer molecules should be accumulated into the tumor cells increasing the drug selectivity. This Ph.D. work is focused on the exploration of several passive DTD methods. The first phase consists in the synthesis of Pt(IV) complexes, containing suitable functionalities to be exploited in coupling reactions with nanosized vectors. Alternatively, Pt complexes can be encapsulated into liposomes. Then, the loading of selected nanocarriers with the metal complexes and the biological evaluation of the resulting conjugates are performed. The developed projects are listed below: - synthesis, characterization of Pt(IV) complexes, their couplings with different types of amino-functionalized nonporous silica NPs and in vitro tests of the resulting conjugates; - coupling reactions of the previously prepared Pt(IV) compounds with chitosan and its derivatives; - synthesis, characterization of Pt(IV) prodrugs able to link magnetic iron oxide NPs and their couplings with such vectors; - encapsulation of antitumor drugs into liposomes and their in vitro studies.

Highly fluorescent conjugated polymers (CPs) are an important class of biomaterials used for various biological applications including labelling, sensing, and delivery of biological substances. Synthetic versatility and tunable emission make CPs a superior class of biomaterials. Understanding the structure-function relationship of CPs plays a vital role in designing high performing biomaterials. The cationic CPs are self-assembled to conjugated polymer nanoparticles (CPNs) in an aqueous environment due to their amphiphilicity. The physical and biophysical properties of CPNs are highly dependent on the chemical functionality and backbone structure of CPs. Modulation of the surface property and backbone structure of CPNs play an important role for efficient internalization of CPNs into cells. The goal of this dissertation is to understand the structure function relationship of CPNs in an aqueous environment and the change in their photo physical properties upon the self-assembly of CPNs with different backbone structure upon complexation with biologically significant polysaccharides and cell membrane. This work presents the self-assembly of a set of four cationic CPs with different connectivity and backbone structure upon complexation with a linear polyanion hyaluronic acid (HA). The study of photo physical properties changes upon the complexation with series of Glycosaminoglycans (GAGs) provides more insight about how the self-assembly behavior of cationic CPs changes upon the exposure to negatively charged polysaccharides. The understanding of the self-assembly of CPNs with negatively charged biologically important macromolecules under in vitro conditions can give us an idea of photophysical property changes of CPNs during the treatment of CPNs in the cellular environment. The study of the interaction of CPNs with cell membranes using scanning ion conductance microscopy (SICM)-based topography, potential mapping, and confocal microscopy imaging is presented. CPNs are able to induce transient pore like feature formation on the cell membrane during the cellular internalization process. A comparative study of cellular labelling and delivery of siRNA of five CPNs with guanidine motif is presented. The subcellular localization and delivery of siRNA were dependent on the side chain hydrophilicity. The CPNs fabricated with hydrophilic aminoethoxyethanol possesses excellent cellular imaging with higher siRNA delivery.

Orientador: Prof. Dr. Fernando Carlos Giacomelli<br>Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Biotecnociência, 2017.<br>O uso de nanopartículas poliméricas vem progressivamente se intensificando nos últimos anos, principalmente em que pese a aplicações na área biomédica. Neste cenário, o foco principal reside na utilização de polímeros biodegradáveis para fabricação de sistemas nanocarregadores de agentes ativos. Particularmente no campo da nanomedicina, a habilidade de se controlar a dimensão de nanopartículas, bem como se entender o perfil de liberação de pequenas moléculas encapsuladas é essencial. Levando-se em conta estas considerações, o objetivo deste trabalho foi fabricar nanopartículas poliméricas biodegradáveis de PCL e PLGA carregadas com a sonda cumarina-6 e analisar as diversas variáveis de formulação a fim de se entender a influência das características estruturais das nanopartículas e a sua relação com o teor encapsulado, eficiência de encapsulação, perfil de liberação e captura celular dos sistemas nanoestruturados. Os sistemas coloidais produzidos foram caracterizados por meio de técnicas de espalhamento de luz dinâmico (DLS), estático (SLS) e eletroforético (ELS) e espectroscopia de fluorescência. A caracterização estrutural detalhada das formulações produzidas sugere que a densidade das partículas, independente das variáveis de formulação, é substancialmente menor do que a densidade dos polímeros sólidos, implicando que as cadeias poliméricas que formam as nanopartículas estão pouco compactadas e por consequência, os sistemas supramoleculares são substancialmente hidratados (os cálculos mostram conteúdos de água formando os agregados entre 72% e 95% volume/volume). As medidas de espectroscopia de fluorescência evidenciaram que é possível produzir sistemas nanocarregadores onde a eficiência de encapsulação atinge valores maiores do que 50%, entretanto, independente das variáveis de formulação, o teor encapsulado nunca ultrapassa 0,4% massa/massa. Acreditamos que os baixos teores de sonda encapsulada estejam essencialmente relacionados a densidade das partículas e a característica de elevada hidratação. As investigações também demonstram que a liberação da sonda encapsulada é essencialmente governada pelo movimento de difusão. Consequentemente, a biodegradabilidade dos poliésteres utilizados na produção dos coloides pode ter efeito apenas na excreção do material polimérico de ambientes biológicos, mas não parece ter efeito no processo de liberação controlada de princípios ativos encapsulados. Por final, foram feitas análises de microscopia de fluorescência e citometria de fluxo para avaliar a influência dos parâmetros estruturais na captura e internalização celular dos sistemas poliméricos nanoestruturados. Os dados mostram que nanopartículas produzidas a partir de tetraidrofurano (THF), portanto maiores parecem ser internalizadas de maneira mais eficiente pelo menos na região de tamanhos investigada. Os dados também mostram serem inconclusivas as influências da hidrofobicidade e carga superficial dos sistemas.<br>The uses of polymeric nanoparticles came intensifying for a period of time, and are being applicable in the biomedical area. In this scenario, the focus is use biodegradable polymers to production of nanocarrier systems of active agents. Particularly in the field of nanomedicine, the ability to control the size of nanoparticles, as well as understanding the release profile of small-encapsulated molecules, is essential. Taking into account these considerations, the objective of this work was to manufacture biodegradable polymeric nanoparticles of PCL and PLGA loaded with the coumarin-6 probe and to analyze the various formulation variables in order to understand the influence of a structural characteristics of nanoparticles, and their relation with the encapsulated content, encapsulation efficiency, release profile and cellular capture of nanostructured systems. The colloidal systems were produced to characterizing by dynamic light scattering (DLS), static (SLS) and electrophoretic (ELS) techniques and fluorescence spectroscopy. The detailed structural characterization of formulations suggested that density of particles, regardless of a formulation variable, is substantially lower than the density of the solid polymers, implying that polymer chains forming the nanoparticles are poorly compacted and consequently the supramolecular systems are substantially hydrated (the calculations show water contents forming the aggregates between 72% and 95% v/v). The fluorescence spectroscopy measurements showed that it is possible to produce nanocarrier systems where the encapsulation efficiency reaches values higher than 50%, however, regardless of the formulation variables; the encapsulated content never exceeds 0.4% w/w. We believe that the low levels of encapsulated probe are essentially related to particle density and the characteristic of high hydration. The investigations also demonstrate that the release of a encapsulated probe is essentially governed by the diffusion movement. According to biodegradability of polyesters used in the production of colloids may have effect only in the excretion of polymer material from biological environment, but does not appear to have an effect on the controlled release process of encapsulated active principles. Finally, fluorescence microscopy and flow cytometer analyzes the performances to evaluate the influence of structural parameters on capture and cellular internalization of nanostructured polymer systems. The data shows that nanoparticles produced from tetrahydrofuran (THF), therefore larger, appear to be internalized more efficient at least in the region of investigation sizes. The data also shows that the influences of the hydrophobicity and surface charge of the systems was inconclusive.

Les polyesters aliphatiques, comme le poly(acide malique) et ses dérivés, sont une famille de polymères aux propriétés de bio(comptabilité) et de bio(dégradabilité) remarquables, qui en font des candidats de choix pour l'élaboration de systèmes de vectorisation de principes actifs. Généralement, ces polymères sont synthétisés via des réactions de polymérisation utilisant des amorceurs, voir des catalyseurs, organiques, organométalliques ou métalliques. La présence de ces molécules, même à l'état de traces, peut être à l'origine d'une toxicité non souhaitée. Par conséquent, l'utilisation de biocatalyseurs, comme les lipases, se développe pour apporter une solution à cet inconvénient. Cependant, cette voie de synthèse enzymatique fait face à d'autres problèmes, tels qu'une polymérisation moins bien maîtrisée et des polymères de masses molaires faibles. Cette thèse a donc pour objectif de mettre au point une voie de polymérisation du malolactonate de benzyle utilisant la lipase de pancréas de porc (PPL) comme amorceur. Dans un premier temps, nous avons optimisé certains paramètres réactionnels permettant d'obtenir des poly(malate de benzyle) , PMLABe, de masses molaires suffisamment élevées pour que ces polymères puissent être utilisés dans la formulation de vecteurs de principes actifs, grâce à l'utilisation et l'extrapolation d'un plan d'expérience. Nous nous sommes ensuite intéressés à la compréhension du mécanisme réactionnel de la polymérisation enzymatique du malolactonate de benzyle, une β-lactone β-substituée. Les différentes études menées ont permis d'approfondir notre connaissance dans ce domaine. Deux mécanismes ont été proposés et des expériences sont en cours pour confirmer l'un d'entre eux. Finalement, comme l'objectif initial est de proposer une méthode de synthèse de dérivés du PMLA plus biocompatibles conduisant à des polymères sans résidus d'amorceurs chimiques toxiques, nous avons comparé les activités biologiques de nanoparticules préparées à partir de PMLABe synthétisés par voie chimique et par voie enzymatique. Pour cela, nous avons mesuré la captation de ces nanoparticules, encapsulant une sonde de fluorescence, par des cellules hépatiques HepaRG. Puis, nous avons évalué la toxicité aiguë et la toxicité chronique de ces nanoparticules vis-à-vis des cellules HepaRG. Ces études ont permis de mettre en évidence certaines propriétés des nanoparticules ayant une influence sur la survie cellulaire et le métabolisme des cellules HepaRG. De la compréhension théorique aux applications potentielles, cette thèse apporte des connaissances sur la polymérisation enzymatique des lactones substituées, un domaine peu décrit dans la littérature<br>Aliphatic polyesters, like poly(malic acid)and its derivatives, are a family of polymers with outstanding properties, such as bio(degradability) and bio(compatibility). Therefore, these polyesters can be considered as excellent candidates for the design of drug carriers. These kinds of polymers are usually synthesized thanks to polymerization reactions using organic, organometallic or metallic initiators or catalysts. The presence of such molecules, even in trace amounts, can cause undesired toxicities. Therefore, the use of biocatalysts, like lipases, is attracting more and more interest and research work to circumvent this problem. However, this enzymatic polymerization method has to face to other issues, such as a lower controlled of the polymerization process and polymers with lower molar masses. Therefore, this PhD research work aimed at setting up the enzymatic polymerization of benzyl malolactonate, using porcine pancreatic lipase (PPL). Firstly, we have optimized some reactional parameters allowing to obtain poly(benzyl malate), PMLABe, with molar masses adapted to their uses for the design of drug carriers, thanks to a Design of Experiments (DoE) and its extrapolation. We were then interested by the comprehension of the enzymatic polymerization mechanism of the benzyl malolactonate. The different studies we carried out allowed us to deepen our knowledges of such enzymatic polymerization. Two non-canonical mechanisms were proposed and further experiments are in progress to confirm the one which is the more probable. Finally, because our initial goal was to propose a more biocompatible polymerization method to obtain PMLABe free of traces of chemical initiator, we compared biologic activities of different nanoparticles prepared from PMLABe synthesized using chemical or enzymatic pathway. For that, we have first measured the uptake of these nanoparticles encapsulating a fluorescent dye, by the hepatic cells HepaRG. Then, we have studied the acute and chronic toxicity of the nanoparticles on the HepaRG cells. Results of these studies have highlighted that certain properties of the nanoparticles and/or of the polymers which constituted them have an influence on the cells viability and on the cells metabolism. From the theoretical mechanism to the probable applications, this thesis brings knowledge about the enzymatic polymerization of substituted lactone, a field poorly described in the literature

Applications of nanotechnology in medicine, also known as nanomedicine, is a rapidly growing field as it holds great potential in the development of novel therapeutics toward treatment of various diseases. Shell crosslinked knedel-like nanoparticles (SCKs) that are self assembled from amphiphilic block copolymers into polymeric micelles followed by crosslinking selectively throughout the shell domain have been investigated as theranostic agents for the delivery of nucleic acids and incorporation of imaging probes. The main focus of this dissertation is to design and develop unique multifunctional bio-synthetic hybrid nanoparticles that can carry agents for radiolabeling, moieties for inducing stealth properties to minimize protein adsorption in vivo, ligands for site-specific targeting, therapeutic payloads, and are optimized for efficient delivery of cargoes intracellularly and to the target sites toward constructing novel nanoscopic objects for therapy and diagnosis. Alteration of polymeric building blocks of the nanoparticles provides opportunities for precise control over the sizes, shapes, compositions, structures and properties of the nanoparticles. To ensure ideal performance of nanoparticles as theranostic agents, it is critical to ensure high intracellular bioavailability of the therapeutic payload conjugated to nanoparticles. Special efforts were made by employing well-defined multi-step polymerization and polymer modification reactions that involved conjugation of peptide nucleic acids (PNAs) to chain terminus of poly(ethylene glycol) (PEG) chain grafts such that they were presented at the outermost surface of SCKs. Additionally, chemical modification reactions were performed on the polymer backbone to integrate positive charges onto the shell of the nanoparticles to afford cationic SCKs (cSCKs) for facilitating cellular entry and electrostatic interactions with negatively charged nucleic acids. Covalent conjugation of F3, a tumor homing peptide, post-assembly of the nanoparticles enhanced cellular uptake and knockdown of nucleolin (a shuttling protein overexpressed at the sites of angiogenesis) and thus inhibiting tumor cell growth. Furthermore, these polymer precursors of the cSCKs were modified with partial to full incorporation of histamines to facilitate their endosomal escape for efficient delivery into the cytosol. The cSCKs were further templated onto high aspect ratio anionic cylinders to form hierarchically-assembled nanostructures that bring together individual components with unique functions, such as one carrying a therapeutic payload and the other with sites for radiolabeling. These higher order nanoobjects enhance circulation in vivo, have capabilities to package nucleic acids electrostatically and contain sites for radiolabeling, providing an overall advantage over the individual components, which could each facilitate only one or the other of the combined functions. Hierarchically-assembled nanostructures were investigated for their cellular uptake, transfection behavior and radiolabeling efficiency, as the next generation of theranostic agents.

Nanomedicine has viewed countless breakthroughs in drug implementation. Nanomaterials have been used to enable enhanced drug delivery to tumor cells with lower toxicity to healthy ones. Controlled Drug Delivery Systems (DDS) have several advantages compared to the traditional forms of drugs. Indeed, when a drug is transported efficiently to the place of action its influence on vital tissues and undesirable side effects can be significantly minimized. Its accumulation at the target site increases and, consequently, the required doses are lower. Different nanoparticles (NPs) have been developed using different polymers with or without surface modification to target tumor cells both passively and/or actively. With this work, it was intended to develop and test polymeric nanoparticles (PNPs), as DDS for anti-cancer therapy. This work focused on the development of Poly(L-lactide-co-caprolactone-co-glycolide) (PLCG) NPs, loaded with Doxorubicin, a drug widely used in cancer therapy. Different surfactants, such as Polyvinyl alcohol (PVA) and Dextran sulfate sodium, were used to have DDS with the optimized properties, in terms of size, superficial charge and colloidal stability, drug loading capacity and release over optimal time window. The structural features and the properties of prepared NPs were characterized with different techniques, including, dynamic light scattering (DLS), microscopy, fluorimetric analysis, thermogravimetric analysis. Moreover, the effects of the developed DDS were also tested on some selected tumorous cellular lines (MCF7) to assess their effectiveness in anti-cancer therapy.<br>A nanomedicina tem sido alvo de incontáveis avanços na implementação de fármacos. Cada vez mais são usados nanomateriais para permitir a libertação de fármacos, diminuindo os efeitos tóxicos nas células saudáveis, aumentando a liberação destes em células tumorais. Sistemas de liberação controlada de fármacos têm várias vantagens em comparação com as formas tradicionais de administração. Um fármaco é transportado para o local de ação, portanto, a sua influência sobre os tecidos vitais e os efeitos colaterais indesejáveis podem ser minimizados. A acumulação de compostos terapêuticos no local alvo aumenta e, consequentemente, as doses necessárias são menores. Diferentes nanopartículas poliméricas têm sido desenvolvidas, usando diferentes polímeros com ou sem modificação de superfície para atingir as células tumorais de forma passiva e/ou ativa. Com este trabalho, pretendeu-se desenvolver e testar nanopartículas poliméricas como sistema de libertação de fármacos para terapia anticancerígena. Este trabalho focou-se no desenvolvimento de nanoparticulas de Poly (L-lactide-co-caprolactona-co-glicolide) (PLCG), carregadas com Doxorrubicina. Foram testados diferentes surfactantes, tais como álcool polivinílico e sulfato de dextrano de sódio, de forma a obter sistemas com propriedades otimizadas, tais como tamanho, carga superficial e estabilidade coloidal, capacidade de carga de fármaco e a eficiência da libertação do fármaco. As características estruturais e as propriedades das nanoparticulas preparadas foram caracterizadas por diferentes técnicas, incluindo dispersão dinâmica de luz, microscopia, análise fluorimétrica, termogravimetria e espectrocopia de infravermelho. Além disso, os efeitos dos nanossistemas desenvolvidos também foram testados em algumas linhas celulares tumorais selecionadas (MCF7) para avaliar a sua eficácia no tratamento do cancro.

Thesis (M.Sc.)--University of Alberta, 2010.<br>A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Pharmaceutical Sciences. Title from pdf file main screen (viewed on February 17, 2010). Includes bibliographical references.