This dissertation describes the use of spherical micro- and nanoparticles as building blocks for the fabrication of colloidal crystals. The polymer component used in all of the projects that are described herein is poly-N-isopropylacrylamide (pNIPAm). The polymeric identity of particles composed of this soft, hydrogel material, which is also thermoresponsive, contributes to particle self-assembly to form ordered structures. Specifically, particles that possess a core/shell topology were investigated to allow for the localization of distinct polymeric properties. Chapter 2 examines a characterization technique using fluorescence resonance energy transfer (FRET) that was explored to investigate the structure of pNIPAm particles that possess this core/shell topology. Chapters 4-6 investigate strategies to impart both stability and flexibility to the particles so that these properties could assist in particle self-assembly as well as provide a stable construct for the production of robust crystalline materials. Styrene was used as the main monomer component in a copolymer synthesis with NIPAm to achieve poly(styrene-co-N-isopropylacrylamide particles (pS-co-NIPAm) that exhibited both hard and soft properties. Simple drying procedures were used to form crystal assemblies with these particles and the application of these pS-co-NIPAm particle suspensions as processable, photonic inks is also investigated. Chapter 7 examines the ability to physically cross-link colloidal crystals composed of pS-co-NIPAm particles by simple heating methods to produce robust films. The optical properties of these crystal films could be tuned by simple rehydration of the film due to the hydrogel character of the crystal building blocks. Chapters 3 and 5 examine the synthesis and self-assembly strategies of core/shell particles using the properties of pNIPAm shell layers that have been added to different types of core particles (silver or pS-co-NIPAm) for the purposes of fabricating colloidal crystals with enhanced properties using thermal annealing procedures. Chapter 8 explores the use of silver particles as tracers for the characterization of colloidal crystals composed of thermally annealed colloidal crystals composed of pNIPAm hydrogel particles.

Controlled drug delivery systems are becoming increasingly interesting with the contribution of nanotechnology. In the case of transdermal applications the greatest limitation is the highly impermeable outermost layer of the skin, the stratum corneum. One promising method of controlled transdermal drug delivery of the skin therapeutics is the use of nanoparticles as carriers. Encapsulation of the drug, as opposed to classical topical application of creams or emulsions, allows the drug to diffuse into hair follicles where drug release can occur in the deeper layers of the skin. The aim of this study was to develop micro and nano sized carriers as drug delivery systems to achieve treatment for skin conditions like psoriasis, aging or UV damage, caused by radiation or health problems. Two different types of bioactive agents, retinyl palmitate (RP) and Dead Sea Water (DSW), were used by encapsulating in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) carriers. In some tests MgCl2 was used as a substitute for DSW when quantification was needed. Bioactive agent loaded nanospheres and nanocapsules were prepared with o/w and w/o/w methods in low micron (1.9 &micro / m), mid nano (426 nm) and nano (166 nm) sizes. Loading, encapsulation efficiency and release kinetics were studied. The encapsulation efficiency and loading values are low especially for the water soluble agents, DSW and MgCl2. It was observed that the capsules loaded with hydrophilic agents released their content in the first 24 h in aqueous media. The encapsulation efficiency and loading values for RP were higher because of the insolubility of the agent in water. In the in vitro studies carried out with L929 mouse fibroblast cells, the nano sized PHBV capsules were detected in the cytoplasm of the cells. Cell viability assay (MTT) for L929 cells showed a growth trend indicating that the particles were not cytotoxic and the values were close to the controls. Hemolytic activity was examined using human erythrocytes and micro/nanoparticles of PHBV were found to be non hemolytic. In vivo testing with BALB/c mice, nanocapsule penetration revealed that a small amount of nano sized particles penetrated the mice skin, despite the highly impermeable outer skin layer. As a result, PHBV micro/nanoparticles have a significant potential for use as topical drug delivery systems in the treatment of skin diseases.

The emerging class of biologic drugs, including proteins, peptides, and gene therapies, are widely administered by injection, despite potential systemic side effects. Rational design of targeted carriers that can be delivered non-invasively, with reduced side effects, is essential for the success of these therapies, as well as for the improvement of patient compliance and quality of life. One potential approach is to take advantage of specific physiological cues, such as enzymes, which would trigger drug release from a drug carrier. Enzymatic cleavage is highly specific and could be tailored for certain diseased tissues where specific enzymes are up regulated. Enzymatically-degradable hydrogels, which incorporate an enzyme- cleavable peptide into the network structure, have been extensively reported for releasing drugs for tissue engineering applications. These studies showed that a rapid response and corresponding drug release occurs upon enzyme exposure, whereas minimal degradation occurs without enzyme. Recently, Michael addition reactions have been developed for the synthesis of such enzymatically-degradable hydrogels. Michael addition reactions occur under mild physiological conditions, making them ideally suited for polymerizing hydrogels with encapsulated biologic drugs without affecting its bioactivity, as in traditional polymerization and particle synthesis. The focus of my research was to create enzymatically-degradable hydrogel microparticles, using Michael addition chemistry, to evaluate for use as an inhalable, disease-responsive delivery system for biologic drugs and nanoparticles. In this dissertation, I utilize bioconjugation and Michael addition chemistries in the design and development of enzymatically-degradable hydrogels, which may be tailored to a multitude of disease applications. I then introduce a new method of hydrogel microparticle, or microgel, synthesis known as the Michael Addition During Emulsion (MADE) method. These microgel carriers were evaluated in vitro, and found to exhibit triggered release of encapsulated biologic drugs in response to enzyme, no significant cytotoxic effects, and the ability the avoid rapid clearance by macrophages. Lastly, in vivo studies in mice were conducted, and microgels were found to exhibit successful delivery to the deep lung, as well as prolonged pulmonary retention after intratracheal aerosol delivery. In conclusion, a new class of enzymatically-degradable microgels were successfully developed and characterized as a versatile and promising new system for pulmonary, disease-responsive delivery of biologic drugs. / text

Recent advances in molecular biology have led to an explosive growth in the number of peptide and protein drugs derived from both recombinant technology and conventional peptide drug design. However, development of peptide and protein therapeutics has proven to be very challenging because of inadequate physical and chemical stability. In recent years, particle engineering processes have become promising approaches for enhancement of protein stability as well as provide options for more delivery routes. In this research program, spray freezing into liquid (SFL) process was developed and optimized in order to achieve broad platform and application in protein and peptide drug delivery systems. The overall goal of this research was to produce stabilized protein and peptide microparticles for various drug delivery systems by using SFL particle engineering technology. Firstly, the use of the SFL process to produce peptide microparticles was investigated. Insulin microparticles produced by the SFL process were highly porous, low tap density and narrow particle size distribution. The influence of the SFL process parameters and excipients on the physicochemical properties of peptide microparticles was determined and compared to the widely used particle formation technique--freeze-drying. The SFL process was further used to produce protein microparticles. In the study, bovine serum albumin (BSA), a medium sized protein, was used as a model drug. The influence of SFL process parameters and excipients on the stability of BSA was studied. Very low monomer loss of BSA was found in this study even though the specific surface area of the powder was very high. Results also demonstrated that the SFL process had minimal influence on protein structure. The SFL process was further investigated by comparing the SFL process to spray freeze drying process (SFD), which is a relatively new process to produce protein and peptide microparticles. The influence of atomization, freezing and drying on the stability of lysozyme was investigated for both the SFL and SFD process. This study tested the hypothesis that the SFL process is a better process than SFD process because of avoiding air-liquid interface and minimum interfacial surface absorption of protein in SFL process. The particle size of protein and peptide microparticles produced by SFL process was further reduced to nanoparticles by sonication or homogenization processes in organic solvent. In this study, the influence of process parameters on the particle size and enzyme activity of lysozyme was investigated. The results showed that sonication or homogenization did not influence the enzyme activity of lysozyme. Lastly, insulin and insulin/dextran microparticles produced by SFL the process was encapsulated into polymer microspheres for oral delivery. Complexation and polymer composition was studied in order to optimize release and stability of insulin. Insulin nanoparticles in microspheres minimized the release of insulin in acid with high drug loading compared to other studies. The stability of insulin was decreased by complexation to dextran sulfate. The results of this research demonstrated that the SFL process offers a highly effective approach to produce protein and peptide powders suitable for different drug delivery systems. The microparticles produced by the SFL process had desirable characteristics such as narrow particle size distribution and high porosity. The stability of protein and peptide was well maintained through the SFL process. Therefore, SFL process is an effective particle engineering process for protein and peptide pharmaceuticals. / text

Advances in medical treatment are leading away from generalized care towards intelligent systems or devices which can sense and respond to their environment. With these devices, the burden of monitoring and dosing for treatment can be removed from the doctor (or the patient) and be placed on the device itself. Implicit closed-loop control systems will allow the device to respond to its environment and release therapeutic agent in response to a specific stimulus. Environmentally responsive hydrogels show great promise in being incorporated in such an intelligent device, such as pH-responsive hydrogels which can swell and deswell in response to changes in the pH of the media. Thus, pH changes can be exploited for controlled and intelligent drug delivery when used in combination with these pH-responsive hydrogels. In this work, heterogeneous, thermal-redox initiated free-radical polymerizations were developed to synthesize novel pH-responsive hydrogels, microparticles, and nanogels. The specific disease of interest was type I diabetes, which requires daily doses of insulin both at a basal amount and either a postprandial or preprandial bolus in order to maintain blood glucose levels within safe limits. To allow pH-responsive hydrogels to be sensitive to glucose, glucose oxidase was incorporated which oxidizes glucose to gluconic acid. A novel inverse-emulsion polymerization method was developed for the synthesis of poly[2-(diethylaminoethyl methacrylate)-grafted-polyethylene glycol monoethyl ether monomethacrylate] (P(DEAEM-g-PEGMMA)) nanogels (100-400 nm) for intelligent insulin delivery. The new polymerization method allowed the incorporation of hydrophilic components, such as glucose oxidase and catalase, as well as PEG surface tethers of lengths 400 Da up to 2000 Da. Surface tethers successfully decreased the surface charge of the nanogels. Insulin loading and release was determined for microparticles which were able to imbibe substantial amounts of insulin from solution when swollen, entrap the insulin when collapsed, and then release the insulin in response to either a pH or glucose stimulus. / text

Protein biomarkers circulating in blood hold the promise of improved diagnosis, prognosis and follow-up of treatment of disease via minimally invasive procedures. For the discovery and validation of such biomarkers, methods are needed that can facilitate parallel, highly specific and in-depth analysis of the blood proteome. The work presented in this thesis intends to develop and apply such assays, building on the concept of the proximity ligation assay (PLA). In paper I, I present an easy and non-expensive alternative for the conjugation of oligonucleotides to antibodies via biotin-streptavidin-biotin interaction. This approach can be used when large sets of antibodies and/or oligos need to be validated for their performance as probes in PLA reactions. In paper II, a solid-phase variant of PLA (SP-PLA) for the detection and quantification of proteins in blood is presented. SP-PLA exhibited an improved limit of detection compared to commercial ELISA assays by two orders of magnitude. In addition SP-PLA exhibited a broader dynamic range by at least one order of magnitude and required only 5 μl of sample, rendering the method very well suited for analyses of precious bio-banked material. Last but not least, SP-PLA was used to validate the diagnostic potential of GDF-15 as a biomarker for cardiovascular disease in a set of cardiovascular disease patients and healthy controls. Paper III discusses the development of a multiplex SP-PLA (MultiPLAy) for the simultaneous detection of 36 proteins in just 5 μl of sample. MultiPLAy exhibited an improved LOD when compared to state-of-the-art bead-based sandwich assays. Most importantly, we observed only a minimal tendency to increased background with multiplexing, compared to a sandwich assay, suggesting that much higher levels of multiplexing will be possible. The assay was used to identify putative biomarkers in sample cohorts of colorectal cancer (CRC) and cardiovascular disease (CVD). Subsequent multivariate analysis revealed previously known diagnostic biomarkers. Furthermore, we successfully applied next-generation sequencing as a readout for the protein assays, allowing for the first time digital recording of protein profiles in blood. In paper IV, we investigated the suitability of prostasomes as blood biomarkers in patients with prostate cancer using a newly developed PLA assay (4PLA) that utilizes five binders for the detection of complex target molecules. The assay successfully detected significantly elevated levels of prostasomes in blood samples from prostate cancer patients prior to radical prostatectomy, compared to controls and men with benign biopsy results.

Recently, considerable attention has been focused on the generation of nano- and micrometer scale multicomponent polymer particles with specifically tailored mechanical, electrical and optical properties. As only a few polymer-polymer pairs are miscible, the set of multicomponent polymer systems achievable by conventional methods, such as melt blending, is severely limited in property ranges. Therefore, researchers have been evaluating synthesis methods that can arbitrarily blend immiscible solvent pairs, thus expanding the range of properties that are practical. The generation of blended microparticles by evaporating a co-solvent from aerosol droplets containing two dissolved immiscible polymers in solution seems likely to exhibit a high degree of phase uniformity. A second important advantage of this technique is the formation of nano- and microscale particulates with very low impurities, which are not attainable through conventional solution techniques. When the timescale of solvent evaporation is lower than that of polymer diffusion and self-organization, phase separation is inhibited within the atto- to femto-liter volume of the droplet, and homogeneous blends of immiscible polymers can be produced. We have studied multicomponent polymer particles generated from highly monodisperse micrordroplets that were produced using a Vibrating Orifice Aerosol Generator (VOAG). The particles are characterized for both external and internal morphology along with homogeneity of the blends. Ultra-thin slices of polymer particles were characterized by a Scanning Electron Microscope (SEM), and the degree of uniformity was examined using an Electron Dispersive X-ray Analysis (EDAX). To further establish the homogeneity of the polymer blend microparticles, differential scanning calorimeter was used to measure the glass transition temperature of the microparticles obtained. A single glass transition temperature was obtained for these microparticles and hence the homogeneity of the blend was concluded. These results have its significance in the field of particulate encapsulation. Also, better control of the phase morphologies can be obtained by simply changing the solvent/solvents in the dilute solutions. Evaporation and drying of a binary droplet containing a solute and a solvent is a complicated phenomenon. Most of the present models do not consider convection in the droplet phase as solvent is usually water which is not very volatile. In considering highly volatile solvents the evaporation is very rapid. The surface of the droplet recedes inwards very fast and there is an inherent convective flow that is established inside the solution droplet. In this dissertation work, a model is developed that incorporates convection inside the droplet. The results obtained are compared to the size obtained from experimental results. The same model when used with an aqueous solution droplet predicted concentration profiles that are comparable to results obtained when convection was not taken into account. These results have significance for more rigorous modeling of binary and multicomponent droplet drying.

Chronic pulmonary disorders, marked by excessive extracellular matrix deposition (ECM) or fibrosis, are the most resistant to present clinical therapies resulting in prognoses of 50% life expectancy three years from diagnosis. Inadequacies of current treatments may be attributable to limitations in non-invasive therapeutic administration modalities. However, with the use of polyketal microparticles (PKMs), a novel drug delivery vehicle, a myriad of therapeutic schemes may be explored. Polyketals are a new polymeric family characterized by tissue biocompatibility, rapid hydrolysis, and benign degradation byproducts making it attuned for pulmonary applications. Potential treatments such as siRNA, oligo nucleotides, enzymes and other biomolecules can be encapsulated within PKMs and administered non-invasively via inhalation. For this study, we selected a model therapeutic peptide, Ac-SDKP, with established anti-fibrotic properties as the load for PKMs. For lung dysfunctions accompanied by fibrotic scarring, Ac-SDKP possesses promise in restoring the normal ECM framework. To assess PKMs viability as a pulmonary drug delivery vehicle three objectives were initially defined: 1) Synthesize particles possessing aerodynamic properties conducive for aerosolization 2) Optimization of the therapeutic load, Ac-SDKP, in PKMs to levels that will translate to clinical dosing concentrations, and 3) Determine the biocompatibility of the PKMs in the lung. Optimization of the Ac-SKDP loading within PKMs and size analysis revealed that a solid in oil in water double emulsion particle synthesis technique produced the most ideal microspheres. Based on previous reports, the loading efficiency attained, when locally dispensed, should reach clinical dosing requirements. Synthesized particles were compatible with aerosolization criteria; i.e., diameters below 3 μm and low polydispersities. In addition, we evaluated PKM tissue biocompatibility using a murine lung model. Examination of bronchoalveolar lavage fluid demonstrated only a slight inflammatory response to intratracheal particle injections of PKMs whereas PLGA, a commonly used biomaterial, elicited a significantly higher response. Histological assessment of the lungs following particle injection verified PKMs biocompatibility superiority. In conclusion, small-diameter PKMs are a suitable delivery system for pulmonary drug delivery, capable of delivering small peptide therapeutics and evading the local inflammatory response. The present work will enable expansion of therapeutic avenues capable of combating chronic lung disease.

Coronary artery disease is a leading cause of morbidity and mortality in developed countries. Percutaneous transluminal coronary angioplasty (PTCA) is an important treatment option when intervention is required; namely for patients with relatively severe occlusions. However, adverse events including recurrence of angina pectoris and restenosis of the treated artery limit patient prognosis, with subsequent re-vascularisation often necessary. Platelet activation accompanies PTCA, with platelet adhesion and aggregation involved in thrombus formation during restenosis. During platelet activation, highly coagulant platelet-derived microparticles (PMPs) are formed, and it is likely that these PMPs will also be produced during PTCA. While platelet aggregation inhibitors used during PTCA limit platelet aggregation and decrease the incidence of restenosis, they do not prevent PMPs being formed. PMPs are capable of adhesion and aggregation, and adhere to PTCA treated arteries in an animal model. Therefore, in order to understand the phenomenon of restenosis and its improved limitation, it is necessary to investigate PMP formation during PTCA. The field of PMP study is in its infancy, with conflicting results from the substantial inequities in methods of PMP measurement, which may be exacerbated by PMP heterogeneity. The current literature on this topic is reviewed in Chapter 2, where the PMP surface and possible functions are considered, and the PMP size and morphology examined. To conclude, the relationship between PMPs and PTCA is explored, with a focus on the potential role of PMPs in restenosis. The knowledge deficiencies in this field are highlighted at the conclusion of this chapter. Very little is known regarding the production of PMPs with PTCA. The level of PMPs during PTCA was monitored in paired arterial blood samples obtained from seventy-five patients undergoing the procedure (Chapter 3). A significant increase in PMPs from baseline to completion of PTCA was clearly demonstrated for the first time. This indicated that procoagulant PMPs are produced during PTCA and may contribute to subsequent restenosis. Furthermore, administration of the platelet aggregation inhibitor abciximab to a group of thirty-eight high risk patients limited PMP formation; given that abciximab patients required more rigorous PTCA, the protective benefit of this medication for PMP production is underlined. Although few patients in this study experienced restenosis, it is interesting to note that of those treated with abciximab, all patients suffering subsequent restenosis were revascularised using PTCA. This demonstrates that their occlusions were comparatively mild as the need for coronary artery bypass grafting was avoided, and suggests that minimisation of PMP levels may assist in limiting the progression of severe restenosis. The increased peripheral level of PMPs predicated investigation of the coronary circulation to determine local events. Although the level of PMPs increased significantly within the coronary arteries of PTCA patients, there was no corresponding increase in the coronary sinus (Chapter 4). This important finding indicated that significant levels of PMPs remained within the coronary circulation, where their ability to adhere, aggregate and accelerate haemostasis may allow them to contribute directly to restenosis. During the time when increased levels of PMPs were being formed, there was no evidence of platelet lysis, which refuted the hypothesis that PMPs are merely membrane fragments of lysed platelets. A wide variation in reported PMP sizes has contributed to the hypothesis that PMPs are heterogeneous. As morphological information can assist in understanding physiology, the final study was designed to investigate platelet morphology from PTCA patients (Chapter 5). Most platelets were activated prior to and following PTCA, with a slight decrease in body size occurring due to PTCA, presumably due to loss of cytoplasm in PMPs being shed as reported in the previous chapter. Importantly, platelet distal pseudopod buds were observed, and these did not alter significantly with PTCA. These buds were probably unformed PMPs, although the exact mechanism of PMP formation remains undetermined. The platelet pseudopods were longer and significantly thinner distally with PTCA, which may be due to movement of cytoplasm into these terminal swellings. In addition, buds or swellings directly on the platelet body were smaller following PTCA, and it is likely these may also be PMPs prior to detachment from the parent platelet. This work has contributed substantially to knowledge of PMPs produced during PTCA. The level of PMPs increased significantly in peripheral arterial samples, with the platelet aggregation inhibitor abciximab preventing this occurrence. This may indicate that functional aggregation receptors are an essential requirement for PMP formation under these conditions. However, it is possible for PMPs to be formed when aggregation is inhibited, and therefore the molecular mechanisms of PMP formation remain unconfirmed. The examination of PMPs from the coronary circulation provided valuable data indicating that PMPs are produced during PTCA but remain within the coronary circulation. As PMPs are capable of adhesion and aggregation, this strongly suggests that PMPs within the coronary circulation would contribute directly to pathogenesis of restenosis, although further investigation on PMPs with PTCA is necessary to confirm this association. The examination of platelet morphology during PTCA indicated that platelets possessed terminal pseudopod swellings, and cell surface swellings. Importantly, the terminal swellings, which are likely to be unformed PMPs, were observed for the first time during PTCA.

Submitted by ALINE EVANGELISTA SANTIAGO null (evalineva@hotmail.com) on 2017-12-19T17:39:39Z No. of bitstreams: 1 DISSERTAÇÃO PDF (1).pdf: 6165905 bytes, checksum: 0fe2e6627556b7a80341cb2a27e96540 (MD5) / Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2017-12-20T13:25:02Z (GMT) No. of bitstreams: 1 santiago_ae_me_bot.pdf: 6165905 bytes, checksum: 0fe2e6627556b7a80341cb2a27e96540 (MD5) / Made available in DSpace on 2017-12-20T13:25:02Z (GMT). No. of bitstreams: 1 santiago_ae_me_bot.pdf: 6165905 bytes, checksum: 0fe2e6627556b7a80341cb2a27e96540 (MD5) Previous issue date: 2017-11-24 / Introdução: A concentração plasmática de citocinas, quimiocinas e micropartículas (MPs) em mulheres com câncer de mama e de ovário é uma forma não invasiva de avaliar a resposta inflamatória/regulatória sistêmica associada a esses tumores e o papel do microambiente formado na resposta pró e antitumoral na paciente. Portanto, o objetivo deste estudo foi comparar o perfil da resposta inflamatória sistêmica do câncer epitelial de ovário (CEO) e do câncer de mama através da medição de citocinas, quimiocinas e MPs, para assim avaliar se existe ou não diferença nesse padrão de resposta inflamatória sistêmica. Métodos: Noventa e quatro mulheres sem evidência de malignidade (n = 30), com câncer de mama (n = 38) ou câncer de ovário epitelial (n = 26) foram avaliadas. Foram coletadas amostras plasmáticas e de tecido tumoral. A avaliação dos marcadores inflamatórios foi realizada pela dosagem de citocinas (IL-1, IL-2, IL-6, IL-10, IL-12, IL-17A, TNF-α e IFN- ), quimiocinas (CXCL8, CXCL -9, CXCL 10, CCL 2, CCL5) e MPs (neutrófilos, leucócitos, monócitos, eritrócitos, células endoteliais, plaquetas e linfócitos) por citometria de fluxo / Cytometric Bead Array. As diferenças entre os grupos foram avaliadas por Kruskal-Wallis. As diferenças com p<0,05 foram consideradas significantes. Resultados: Os níveis plasmáticos das citocinas pró-inflamatórias IL-6 (p=<0,001), TNF-α (p=0,004) e IL-12 (p=0,0019) foram significativamente maiores em pacientes com câncer de ovário em comparação com as mulheres com câncer de mama e com o grupo controle. Pacientes com câncer de ovário foram também associadas a maiores níveis de IL-10 (p<0,001) e das quimiocinas CXCL-9 (p<0,001) e CXCL-10 (p<0,001) em comparação aos outros grupos. Os níveis de MPs derivados de neutrófilos aumentaram significativamente em amostras plasmáticas de pacientes com CEO em comparação com mulheres com câncer de mama e do grupo controle (p<0,001). Em contraste, as MPs derivadas de células endoteliais foram menores nas pacientes com CEO em comparação com os demais grupos (p=0,0491). Houve um equilíbrio entre citocinas, quimiocinas e MPs nos grupos de câncer de mama e controle. A rede de citocinas e quimiocinas inflamatórias/regulatórias em pacientes com CEO apresentou maior complexidade em relação aos demais grupos e com fortes interações nas redes entre fatores inflamatórios e imunológicos plasmáticos. Esta rede incluiu mais biomarcadores associados com correlações negativas e positivas entre eles. Conclusão: Este estudo é uma pesquisa promissora e original. Os resultados podem refletir as discrepâncias entre a carcinogênese no câncer de ovário e de mama, sugerindo um padrão inflamatório sistêmico maior no CEO. MPs podem servir como uma nova fonte de informação relacionada à doença. / Introduction: The plasma concentration of cytokines, chemokines and microparticles (MPs) in women with breast and ovarian cancer is a noninvasive way of assessing the systemic inflammatory / regulatory response associated with these tumors and the role of the microenvironment formed in the pro and antitumor response in the patient. Therefore, the objective of this study was to compare the profile of the systemic inflammatory response of epithelial ovarian cancer (EOC) and breast cancer by measuring cytokines, chemokines and MPs, in order to evaluate whether or not there is a difference in this pattern of inflammatory response systemic. Methods: Ninety-four women with no evidence of malignancy (n = 30), breast cancer (n = 38) or epithelial ovarian cancer (n = 26) were evaluated. Plasma samples and tumor tissue were collected. The evaluation of inflammatory markers was performed by the measurement of cytokines (IL-1, IL-2, IL-6, IL-10, IL-12, IL-17A, TNF-α and IFN-), chemokines (CXCL8, CXCL -9, CXCL 10, CCL 2, CCL 5) and MPs (neutrophils, leukocytes, monocytes, erythrocytes, endothelial cells, platelets and lymphocytes) by flow cytometry / Cytometric Bead Array. The differences between the groups were assessed by Kruskal-Wallis. Differences with p <0.05 were considered significant. Results: Plasma levels of the proinflammatory cytokines IL-6 (p = 0.001), TNF-α (p = 0.004) and IL-12 (p = 0.0019) were significantly higher in ovarian cancer patients compared to women with breast cancer and the control group. Patients with ovarian cancer were also associated with higher levels of IL-10 (p <0.001) and CXCL-9 (p <0.001) and CXCL-10 (p <0.001) chemokines compared to the other groups. Levels of MPs derived from neutrophils increased significantly in plasma samples of EOC patients compared to women with breast cancer and the control group (p <0.001). In contrast, MPs derived from endothelial cells were lower in patients with EOC compared to the other groups (p = 0.0491). There was a balance between cytokines, chemokines and MPs in the breast cancer and control groups. The network of inflammatory / regulatory cytokines and chemokines in patients with EOC presented greater complexity in relation to the other groups and with strong interactions in the networks between inflammatory and immunological plasmatic factors. This network included more biomarkers associated with negative and positive correlations between them. Conclusion: This study is a promising and original research. The results may reflect the discrepancies between carcinogenesis in ovarian and breast cancer, suggesting a higher systemic inflammatory pattern in the EOC. MPs can serve as a new source of disease-related information.