Development of 2-oxazoline-based hydrogels and porous polyester microparticles in scCO2

Thesis submitted to Faculdade de Ciências e Tecnologia from Universidade Nova de Lisboa in partial fulfillment of the requirements for the obtention of the degree of Master of Science in Biotechnology

Preparation of gas-filled porous microparticles (GPPs) and microbubbles (MBs) by PGSS method

Dissertation to obtain the Master Degree in Biotechnology

Development of chitosan-based microparticles for pulmonary drug delivery

Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica

On the hydrogeology of the Lower Tagus Basin and its Cenozoic geologic evolution

The chemical features of the ground water in the Lower Tagus Cenozoic deposits are strongly influenced by lithology, by the velocity and direction of the water movement as well as by the localization of the recharge and discharge zones. The mineralization varies between 80 and 900 mg/l. It is minimal in the recharge zones and in the Pliocene sand and maximum in the Miocene carbonated and along the alluvial valley. Mineralization always reflects the time of permanence, the temperature and the pressure. The natural process of water mineralization is disturbed in agricultural areas because the saline concentration of the infiltration water exceeds that of the infiltrated rainwater. In the discharge zones, the rise of the more mineralized, some times thermal deep waters related to tectonic accidents give rise to anomalies in the distribution of the aquiferous system mineralization model. The diversity of the hydrochemical facies of the ground water may be related to several factors whose identification is some times difficult.

Development of composite particles for pulmonary delivery

In this work, biocompatible and biodegradable poly(D-L-lactide-co-glycolide) (PLGA) microparticles with the potential for use as a controlled release system of vaccines and other drugs to the lung were manufactured using supercritical CO2, through the Supercritical Assisted Atomization (SAA) technique. After performing a controlled variance in production parameters (temperature, pressure, CO2/solution flow ratio) PLGA microparticles were characterized and later used to encapsulate active pharmaceutical ingredients (API). Bovine serum albumin (BSA) was chosen as model protein and vaccine, while sildenafil was the chosen drug to treat pulmonary artery hypertension and their effect on the particles characteristics was evaluated. All the produced formulations were characterized in relation to their morphology (Morphologi G3 and scanning electronic microscopy (SEM)), to their physical-chemical properties (X-ray diffraction (XRD, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR)) and aerodynamic performance using an in vitro aerosolization study – Andersen cascade impactor (ACI) - to obtain data such as the fine particle fraction (FPF) and the mass median aerodynamic diameter (MMAD). Furthermore, pharmacokinetic, biodegradability and biocompatibility tests were performed in order to verify the particle suitability for inhalation. The resulting particles showed aerodynamic diameters between the 3 and 5 μm, yields up to 58% and FPF percentages rounding the 30%. Taken as a whole, the produced microparticles do present the necessary requests to make them appropriate for pulmonary delivery.