Chitosan-based nanoparticles and microparticles
Nasti, Alessandro (2008) Chitosan-based nanoparticles and microparticles. [Tesi di dottorato] (Inedito)
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Chitosan-Triphosphate Nanoparticles There is a widespread interest in the use of nano-carriers for drug delivery and chitosan is one of the most sought-after components for designing biocompatible nanoparticles. Here, using a rational experimental design, I have studied the influence of a number of variables (pH, concentrations, ratios of components, different methods of mixing) in the preparation of chitosan/triphosphate (CS/TPP) nanoparticles and in their coating with hyaluronic acid (HA). The aim was to minimise size polydispersity, maximise zeta potential and long-term stability, and control the average nanoparticle size. As a result, three kinds of optimised nanoparticles have been developed, two uncoated and one HA-coated. Their toxicity on fibroblasts and uptake by macrophages have been evaluated. Experiments showed the beneficial character of HA-coating in the reduction of toxicity (IC50 raised from 0.7-0.8 mg/mL to 1.8 mg/mL) and suggested that the uncoated chitosan/TPP nanoparticles had toxic effects following internalisation rather than membrane disruption. Uptake tests were performed after the conjugation of fluorescein isothiocyanate (fluorescent label) with chitosan. The nano-carrier can be produced in future for the delivery of short sequences of RNA (e.g. siRNA), be trackable and rather have the ability to specifically bind to target cells. Chitosan-Triphosphate microparticles Monodisperse microparticles were produced using the Inotech® encapsulator exploiting the gelation between chitosan and TPP. The target of 300 µm size was obtained through optimising several parameters (nozzle oscillation, nozzle diameter, pH, concentrations, flow rate, electrostatic charge). TPP was chosen for its non-toxicity and fast gelling ability. The method was mild and did not require organic solvents or toxic cross-linking reagents. These particles will be used in future experiments to embed hydrophobic actives, proteins or living cells.
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