Design of Lipid Nanoparticles Containing Isavuconazole In-Vitro Characterization and In-Vivo Efficacy Studies
Project no. 22806 · Status: Kapanmış · 2021
Summary
<p>Fungal keratitis is a type of stromal keratitis that develops as a result of a fungal infection in the cornea that is difficult to diagnose and treat, leading to blindness if left untreated. Fungal keratitis has the possibility of perforating the cornea and can lead to irreversible changes. Fungal keratitis accounts for 40 - 50% of all isolated keratitis cases. Therefore, early diagnosis and prompt treatment are essential to prevent long-term complications.</p><p><br></p><p>Agents used in fungal keratitis are Natamycin, Amphotericin B and Voriconazole. However, the use of these preparations is limited due to the side effects of the active ingredients used and the short residence time of the preparation in the eye. Isavuconazole is the newest second-generation triazole antifungal with broad-spectrum antifungal activity to receive US Food and Drug Administration (FDA) approval for the treatment of both invasive aspergillosis and invasive mucormyosis. Isavuconazole is a lipophilic antifungal agent with poor water solubility. The low solubility of isavuconazole in water is the biggest obstacle to the development of the formulation. Therefore, the aim of this study is to prepare lipid-based nanoparticulate systems presented in the form of eye drops.</p><p><br></p><p>To summarize, the aim of this project is to design effective formulations against fungal keratitis, whose surface is modified with collagen to be prepared, which can penetrate the corneal tissue more by loading isavuconazole into SLN or NLC. We have not found any SLN and NLC formulation studies loaded with isavuconazole and modified with collagen using DSPE-PEG. This research will be a pioneering study in this sense. Characterization, release, cell culture and in-vivo studies will be conducted. The effects of the formulation at the molecular level will also be examined.</p>