Development of chitosan-based microparticles for pulmonary drug delivery

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

In this work, novel chitosan (CHT) based microparticles were prepared using supercritical assisted atomization (SAA) and evaluated as potential carriers for sustained pulmonary drug delivery. CHT is a polysaccharide comprising of glucosamine and N-acetylglucosamine units, it is biodegradable, biocompatible and non-toxic being an interesting choice to be used as a drug carrier for inhalation therapy and belongs to the group of swellable polymers. By utilizing SAA, spherical microparticles containing a sharp particle distribution were successfully produced. Ibuprofen (IBP) and bovine serum albumin (BSA) were tested as a model small drug and as a model protein, respectively, to assess the effect on particle size and morphology when co-atomized with CHT on the SAA apparatus. The strategy developed in this work was to produce drug loaded microparticles with suitable aerodynamic characteristics that attain large geometric diameters when in contact with the lung physiological fluids by polymer swelling, reducing macrophage clearance. The microparticles produced by this method were characterized by using Morphologi G3 and Scanning electron microscopy (SEM) to assess their size distribution and morphology. To characterize the solid state properties of the particles X-ray diffraction (XRD), differential scanning calorimetry DSC and Fourier transform infrared (FTIR) were used. Porosity and surface area were determined by mercury and nitrogen porosimetry. In vitro aerosolization studies using an Andersen Cascade Impactor (ACI) were performed to determine the average emitted fraction (EF%) and the fine particle fraction (FPF). Drug-release profiles were determined by in vitro experiments at physiological pH and temperature conditions. The results obtained in this work show that SAA can be successfully used to prepare chitosan based formulations with adequate respirable fractions and sustained release of different bioactive molecules to be administered to the deep lung using dry powder inhalers (DPI).

Fundação para a Ciência e Tecnologia - contracts PEst-C/EQB/LA0006/2011, PTDC/EQU-EQU/116097/2009, Conselho de Reitores das Universidades Portuguesas (CRUP) through Luso-German Agreement A - 13/ 10 and from Fundação Calouste Gulbenkian is acknowledged