Accessibility to nanocapsule loadings
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Abstract
In the present thesis, we highlighted the diverse benefits of nanocapsules for non invasive imaging and drug delivery. Semi-crystalline nanocapsules were synthesized to enable a higher loading capacity in the nanocapsules. The nanocapsules shell was found to create a space confinement for the crystallization. The degree of crystallinity was tuned by varying the shell thickness of the nanocapsules and by the molecular structure of the polymer. With increasing degree of crystallinity, the diffusion of a fluorescent dye, used as a model compound, was found to be reduced.
Semi-crystalline nanocapsules were used to encapsulate a commercial magnetic resonance imaging (MRI) contrast agent with remarkably high loading capacities (up to a theoretical contrast agent concentration inside the nanocapsules of ~0.2 mol L–1) and a relaxivity as high as ~40 s–1 mmol–1 L. The amount of contrast agent needed for the enhancement in tissue contrast was efficiently reduced by the encapsulation of the contrast agent into semi-crystalline nanocapsules compared to free contrast agent.
For computed tomography (CT) measurements, even higher concentrations of contrast agents are required in comparison to MRI experiments. Nanoparticles containing a commercial CT contrast agent were synthesized. The balance between entrapment efficiency and hydrophilicity was controlled to obtain a maximum iodine concentration in dispersion (up to ~12 g of iodine L–1).
To enable an enzymatic triggered release of cargos, proteins were incorporated into nanocapsules as predetermined breaking points. To avoid uncontrolled cell uptake, hydroxyethylstarch was chosen as basic material for the nanocapsules. The release of a dye upon enzymatic degradation was monitored. The more protein was incorporated into the nanocapsule shell, the more fluorescent dye was released upon enzymatic degradation during dialysis. STAT3 inhibitors (Signal Transducer and Activator of Transcription3 inhibitors) were chosen as a model drug. Cell experiments revealed no toxicity and no cell uptake of the nanocapsules.
This thesis gives an insight in how nanocarriers can serve as contrast agents and as nanocarriers for drug delivery. With this method, versatile and non toxic nanoscale contrast agents were obtained. Furthermore, the nanocapsules can also serve as sensitive probes because the relaxivity of MRI contrast agents is strongly dependent on the water exchange in its environment.