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

Histerese térmica de sistemas magnéticos nanoestruturados

We report a theoretical investigation of thermal hysteresis in magnetic nanoelements. Thermal hysteresis originates in the existence of meta-stable states in temperature intervals which may be tuned by small values of the external magnetic field, and are controlled by the systems geometric dimensions as well as the composition. Two systems have been investigated. The first system is a trilayer consisting of one antiferromagnetic MnF2 film, exchange coupled with two Fe lms. At low temperatures the ferromagnetic layers are oriented in opposite directions. By heating in the presence of an external magnetic field, the Zeeman energy induces a gradual orientation of the ferromagnets with the external field and the nucleation of spin- op-like states in the antiferromagnetic layer, leading eventually, in temperatures close to the Neel temperature, to full alignment of the ferromagnetic films and the formation of frustrated exchange bonds in the center of the antiferromagnetic layer. By cooling down to low temperatures, the system follows a different sequence of states, due to the anisotropy barriers of both materials. The width of the thermal hysteresis loop depends on the thicknesses of the FM and AFM layers as well as on the strength of the external field. The second system consists in Fe and Permalloy ferromagnetic nanoelements exchange coupled to a NiO uncompensated substrate. In this case the thermal hysteresis originates in the modifications of the intrinsic magnetic