A novel methacrylate based nanogel system has been designed and developed for drug delivery applications. Methacrylates are optimal tuneable materials in terms of polarity, with combination of hydrophobic and hydrophilic moieties. Synthesis of these nanogels (NGs) was achieved via high dilution radical polymerisation using 2-(tert-butylamino)ethyl methacrylate (tBAEMA) as functional monomer, methacrylic acid (MAA) or ethylene glycol methyl ether methacrylate (EGMMA) as co-monomer and N,N'-methylenebis(acrylamide) (MBA) as cross-linker. Fabricated nanoparticles (NPs) were shown to possess water solubility higher than 2 mg/mL and diameter ranging from 5 to 20 nm (depending on nanogels' composition) as confirmed by either dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, nanogels produced have shown the ability to be employed as Pickering-Ramsden emulsion stabiliser. Their reduced size together with their emulsion capabilities make these nanoparticles a promising system for drug delivery, in particular taking into account skin as administration route. The size is in fact small enough to favour their penetration through the stratum corneum. Furthermore, in the view of their ability to form emulsions, nanogels could be used both as drug carrier and emulsifier in a final pharmaceutical formulation. NGs proved to be able to incorporate both small molecule such as fenoprofen (an anti-inflammatory non-steroidal drug) and big macromolecule such as siRNA. Cytotoxicity and cell metabolism were also evaluated by transfecting normal human dermal fibroblasts (NHDF), keratinocytes (HaCaT) and HeLa cells with nanogels. Data showed that nanoparticles did not affect viability, cells' morphology and adenosine triphosphate (ATP) levels up to high concentration of 100 μg/mL. In addition, preliminary studies indicated the ability of the nanogels to internalise and release their payload inside cells. In conclusion, the results confirmed that this novel system possesses all the desired characteristics to be used as a promising platform for drug delivery.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:765813 |
| Date | January 2016 |
| Creators | Chianello, Giorgio |
| Publisher | Queen Mary, University of London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://qmro.qmul.ac.uk/xmlui/handle/123456789/24565 |
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