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Functional soft nanotubes for drug delivery applications

(2017)

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Vercauteren_30621200_2017.pdf
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Abstract
This work aimed to build polyelectrolyte nanotubes bearing in mind future drug delivery applications. Such structures are obtained by combining Layer-by-Layer assembly, a material deposition technique, with template synthesis, using a nanoporous polycarbonate membrane as template. Two different systems were studied: one comprised of synthetic polyelectrolytes, namely poly(allylamine hydrochloride) (PAH) and poly(sodium 4-styrenesulfonate) (PSS), and one comprised of semi-natural polyelectrolytes, namely chitosan (CHI) and hyaluronan (HA). These two systems were chosen for the purpose of building core-shell structures. In the present work, the effect of several assembling conditions was studied for both systems in order to gain a better understanding of their respective properties. Firstly, PAH/PSS multilayers were built with varying ionic strength and pH. Even the lowest salt concentration chosen for the PE solutions resulted in thicker layers compared to zero ionic strength. However, a negligible influence was found for small concentration increases. For pH, only a small variation was investigated and it was found to cause no effect on the thickness or on the morphology of the nanotubes. The stability of the nanotubes after a prolonged contact with water was also explored. It was noted that, although there is a slight loss in rigidity at first, the PAH/PSS nanotubes remain stable when stored in water for longer periods of time. The same investigations were then performed on CHI/HA multilayers. Ionic strength was observed to cause opposing effects for flat and nanoporous substrates. It led to thicker layers for nanotubes, but the effect was more complex for flat films: for low ionic strength there was an increase in layer thickness, yet for higher values, there was a loss of thickness, suggesting that the critical salt concentration was reached. Variations in the assembling pH are in line with the ionisation curves found in the literature, creating thinner layers at pH 5 and thicker ones at pH 4 and 6. In terms of stability in water, CHI/HA nanotubes were found to lose a great deal of rigidity upon contact with water, even more for tubes assembled at pH 6. For prolonged storage in aqueous solution, further losses of rigidity and changes in morphology were observed only in the first 24 hours. Finally, the cross-linking of the multilayers was investigated in order to increase the nanotubes rigidity in water, but no effect was noticed for the chosen concentrations of EDC and sulfo-NHS. Although some assembling parameters require further explorations before entirely understanding the studied systems properties, this work still paves the way for further investigations involving core-shell nanotubes comprised of the two systems described above.