Polysaccharide - based nanoparticles for drug delivery

The preparation method used for particles formation was the ionotropic gelation, where an ionic interaction between the cationic polymer (chitosan or its derivatives) and the anionic tripolyphosphate (TPP) occurred. Since proteins are very labile molecules, sensitive to several stress factors, this mild preparation method is very suitable to prepare protein loaded nanocarriers. Three model proteins were loaded on nanoparticles, bovine serum albumin (BSA), ovalbumin (OVA) and human insulin (HI), resulting in a good loading efficiency, at least over 50%. Chitosan nanoparticles were prepared and optimized in terms of particle shape and morphology, size distribution, surface chemistry, biocompatibility, production automatization and storage. The average diameter is 200 nm and surface charge is 25 mV. Particle size distribution curve showed the presence of a bimodal population composed of a fraction of small particles (around 40 nm) and a second population around 250 nm. Analysing the evolution of particles formation, a rearrangement of particles can be noticed after TPP addition, with small particles that aggregated with time to form a more homogeneous population of larger particles. Particles were stored for 4 weeks to study their stability in time, resulting in a slight increase of size due to a continuous rearrangement of small particles. Moreover, storage of nanoparticles has been investigated using lyophilization and spray-dryer. Three different bioprotectants have been added to chitosan samples, namely trehalose, mannitol and PEG, preventing their agg