ESSENTIAL OIL NANOEMULSIONS AND CYCLODEXTRIN-BASED PRODUCTS FOR DIMETHYL FUMARATE NASAL DELIVERY

This doctoral thesis investigates nose-to-brain drug delivery systems for administration of dimethyl fumarate (DMF) for the treatment of multiple sclerosis (MS). In the first part, a systematic study was designed for the optimization of nanoemulsions (NEs) encapsulating a neuroprotective essential oil derivative, Carvacrol, along with DMF. The NEs were found to be stable over a period of 3 months with a mean size around 200 nm and PDI below 0.5. Moreover, permeability studies through RPMI 2650 nasal cell lines validated the potential of NEs to release both the drug and essential oil across the nasal epithelium. In the next part, aqueous solubility of DMF was enhanced up to 66% by complexation with sulfobutylether-β-cyclodextrin (SBE-β-CD). Later, this complex was encapsulated in a poloxamers-based thermosensitive gel intended for intranasal drug administration. Rheological analysis ensured that the formulation converts to gel form within the nasal temperature range (30-35 °C). Moreover, viscosity and mucoadhesive analyses demonstrated optimum results for intranasal application. In the last part of the thesis, CV- and stearic acid-based blank nanostructured lipid carriers (NLCs) were prepared. It was observed that formulations containing 5 - 10% (w/w) of solid lipids resulted in stable nanoscale systems, whereas concentrations higher than 10% (w/w) led to precipitation when CV was used as the liquid lipid.