Vecchione, Raffaele (2013) Biodegradable Nanocapsules produced via Layer-by-Layer Technique on Oil based Templates. [Tesi di dottorato]

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Abstract

In this work we focused the attention on the development of nanocapsules like carriers for their capability to embed high payloads of active substances. Moreover we just used natural materials like vegetal oils and natural polysaccharides to avoid side effects from the use of such nanocarriers. In particular, we chose to start from an oil core template for the preparation of nanocarriers to be used in bio-nano-technology fields. Indeed, oil in water emulsions can easily reach sizes down to 100nm making these systems very interesting from a nanotechnology point of view. Then, there is strong need to load and vehicle lipophilic active substances and drugs in order to face their scarce solubility in water which typically prevents an effective bio-distribution of such molecules. Moreover, it is possible to use vegetal oils and natural surfactants like the soybean and the Lipoid E80 used in this work. Typically, the widespread use of oil carriers in the above said fields is generally limited or prevented by the intrinsic instability of immiscible systems like an emulsion. Herein we have been able to stabilize oil in water emulsions of controlled sizes from 200 to down to 70 nm by decorating them with a biodegradable polymer and by implementing a new multi-dispersion processing. Both emulsions preparation and polymer coated emulsion re-dispersion were carried out by using a high pressure homogenizer at 2000 and around 700bar respectively. Stabilities tunable from few weeks to more than one year were obtained depending on polymer concentration. The higher the polymer concentration is, the higher the stability. These stabilized emulsions already interesting by their own for a wide range of applications were also proved to be suitable templates for the built up of more complex systems like multi-layer based nanocapsules. In particular it was demonstrated the capability to prepare monodisperse biodegradable polymer multi-layer by using the layer by layer technique both on low term stability emulsions and on long term stability emulsions. To make possible the deposition on latter emulsions it was developed a novel method of purification which is mediated by the use of magnetic nano-beads magnetically separated after picking up the excess of polymer in solution. These biodegradable polymer nanocapsules can have a huge impact on the development of new carriers for cancer treatment for a series of advantages such as high payload of lipophilic drugs, possibility to easily functionalize them for active targeting, long circulation in the blood, penetration capability, embed tracers for imaging and so on. Moreover, looking at the possible use of these nanocapsules as carriers to be injected in the blood, polymers have been successfully modified in order to be cross-linked once coupled in the multilayer to provide stability against the oxidizing environment in the blood itself. Finally it was proved capability to use such stabilized template to build a silica layer as outer shell. This is a very interesting bio-interface recognized for its biocompatibility, capability to be functionalized as well as the previous polymeric capsules for a possible use in theranostics. One important aspect emerged in this work is that by assessing the capability to use nano-emulsions stable over time for times comparable to the stable inorganic templates we are opening a fascinating scenario in the templating synthesis. Indeed oil template does not need to be removed, which is risky for the capsule, especially in the case of small sizes and natural polymers, and time consuming; capsules can be pre-loaded with high payloads of scarcely or no soluble bio-molecules, drugs, tracers and so on.

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