Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB

Modelos de condutividade térmica em rochas silicáticas, com ênfase em rochas da província Borborema, NE do Brasil

A practical approach to estimate rock thermal conductivities is to use rock models based just on the observed or expected rock mineral content. In this study, we evaluate the performances of the Krischer and Esdorn (KE), Hashin and Shtrikman (HS), classic Maxwell (CM), Maxwell-Wiener (MW), and geometric mean (GM) models in reproducing the measures of thermal conductivity of crystalline rocks.We used 1,105 samples of igneous and metamorphic rocks collected in outcroppings of the Borborema Province, Northeastern Brazil. Both thermal conductivity and petrographic modal analysis (percent volumes of quartz, K-feldspar, plagioclase, and sum of mafic minerals) were done. We divided the rocks into two groups: (a) igneous and ortho-derived (or meta-igneous) rocks and (b) metasedimentary rocks. The group of igneous and ortho-derived rocks (939 samples) covers most the lithologies de_ned in the Streckeisen diagram, with higher concentrations in the fields of granite, granodiorite, and tonalite. In the group of metasedimentary rocks (166 samples), it were sampled representative lithologies, usually of low to medium metamorphic grade. We treat the problem of reproducing the measured values of rock conductivity as an inverse problem where, besides the conductivity measurements, the volume fractions of the constituent minerals are known and the effective conductivities of the constituent minerals and model parameters are unknown. The key idea was to identify the model (and its associated estimates of effective mineral conductivities and parameters) that better reproduces the measures of rock conductivity. We evaluate the model performances by the quantity  that is equal to the percentage of number of rock samples which estimated conductivities honor the measured conductivities within the tolerance of 15%. In general, for all models, the performances were quite inferior for the metasedimentary rocks (34% <  < 65%) as compared with the igneous and ortho-derived rocks (51% <  < 70%). For igneous and ortho-derived rocks, all model performances were very similar ( = 70%), except the GM-model that presented a poor performance (51% <  < 65%); the KE and HS-models ( = 70%) were slightly superior than the CM and MW-models ( = 67%). The quartz content is the dominant factor in explaining the rock conductivity for igneous and ortho-derived rocks; in particular, using the MW-model the solution is in practice vi UFRN/CCET– Dissertação de mestrado the series association of the quartz content. On the other hand, for metasedimentary rocks, model performances were different and the performance of the KEmodel ( = 65%) was quite superior than the HS ( = 53%), CM (34% <  < 42%), MW ( = 40%), and GM (35% <  < 42%). The estimated effective mineral conductivities are stable for perturbations both in the rock conductivity measures and in the quartz volume fraction. The fact that the metasedimentary rocks are richer in platy-minerals explains partially the poor model performances, because both the high thermal anisotropy of biotite (one of the most common platy-mineral) and the difficulty in obtaining polished surfaces for measurement coupling when platyminerals are present. Independently of the rock type, both very low and very high values of rock conductivities are hardly explained by rock models based just on rock mineral content.

Tratamento de argila montmorilonítica para a produção de nanocompósitos poliméricos com retardo de propagação de chama

Compared to conventional composites, polymer matrix nanocomposites typically exhibit enhanced properties at a significantly lower filler volume fraction. Studies published in the literature indicate t hat the addition of nanosilicate s can increase the resistance to flame propagation in polymers. In this work, a treatment of montmorillonite (MMT) nano clay and the effect of its ad dition o n flame propagation characteristics of vinyl ester were studied. The resea rch was conducted in two stages. The first stage focused on the purification and activation of the MMT clay collected from a natural deposit to improve compatibility with the polymer matrix . Clay modification with sodium acetate was also studied to improve particle dispersion in the polymer. The second step was focused on the effect of the addition of the treated clay on nanocomposites ’ properties. Nanocomposites with clay con tents of 1, 2, 4 wt. % were processed. T he techniques for the characterization of the clay included X - ray fluorescence (XRF), X - r ay d iffraction (XRD), thermogravimetric a nalysis (TGA), d ifferential scanning c alorimetry (DSC) , s urface area (BET) and Fourier transform infrared spectroscopy (FTIR). For t he characterization of the nanocomposites , the techniques used were thermogravimetric a nalysis (TGA) , differential scanning c alorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) , scanning electron mi croscopy (SEM), transmission electron m icroscopy (TEM), and the determination of tensile strength, modulus of elasticity and resistance to flame propagation. According to the results, the purification and activation treatment with freeze - drying used in thi s work for the montmorillonite clay was efficient to promote compatibility and dispersion in the polymer matrix as evidenced by the characterization of the nanocomposite s . It was also observed that the clay modifica tion using sodium acetate did not produce any significant effect to improve compatibilization of the clay with the polymer. The addition of the treated MMT resulted in a reduction of up to 53% in the polymer flame propagation speed and did not affect the mechanical tensile strength and modulus o f elas ticity of the polymer, indicating compatibility between the clay and polymer. The effectiveness in reducing flame propagation speed peaked for nanocomposites with 2 wt. % clay, indicating that this is the optimum clay concentration for this property. T he clay treatment used in this work enables the production of vinylester matrix nanocomposites with flame - retardancy properties .