Development and evaluation of topical delivery systems for use in the treatment of psoriasis

Psoriasis is an erythematous, squamous, chronic inflammatory skin disease that affects 2-5% of the world's population and is usually localized on the elbows, knees, scalp and nails. Topical delivery systems to be used in the treatment of psoriasis should be developed considering the lipid disorder of the skin, its excessively dehydrated and thickened structure. Statins are lipid-lowering agents that inhibit cholesterol biosynthesis by inhibiting HMG-CoA reductase. Recent studies have shown that statins have anti-inflammatory and immunomodulatory effects that may be beneficial in various autoimmune diseases, including psoriasis. In this doctoral thesis, the preparation and optimization of the transethosomes and nanostructured lipid carrier systems of fluvastatin sodium were performed. Transethosomes and NLCs were characterized by evaluating particle size, polydispersity index, zeta potential, encapsulation efficiency, pH, conductivity, stability, and structure analysis with ATR-FTIR and DSC, and morphological properties with TEM and SEM. After in vitro penetration studies performed with selected formulations, the accumulation of fluvastatin sodium in the dermal layers was investigated by tape stripping. The effects of delivery systems on the skin were evaluated by ATR-FTIR spectroscopy. The accumulation, localization and penetration pathways of the active substance in different layers of the skin were visualized by confocal laser microscope studies. The cytotoxicity and antipsoriatic activities of the carrier systems loaded with fluvastatin sodium, which had the highest accumulation in the dermal layers, were evaluated by in vitro cell culture studies. Finally, gel formulations of selected transethosomes and nanostructured lipid carrier systems were prepared and their characterizations were performed. Likewise, the accumulation of fluvastatin sodium in the dermal layers by penetration studies and the effects of formulations on skin lipids were investigated by ATR-FTIR analysis. As a result, innovative drug delivery systems loaded with fluvastatin sodium have been developed, which has been proven to be effective in the treatment of psoriasis by in vitro cell studies, is compatible with the skin, is stable, and increases the effectiveness by localizing the active substance in the target area of the skin.