Date of Award
1-1-2022
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
Soumyajit Majumdar
Second Advisor
Walt Chambliss
Third Advisor
Eman Ashour
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Fungal keratitis is a fungal infection of the cornea. Untreated ocular infections can damage the unique, delicate structures of the eye leading to blindness and visual impairments. It primarily affects the corneal epithelium and stroma, although the endothelium and anterior chamber of the eye may get involved in more severe disease. Amphotericin B (AMB) is a macrocyclic polyene that poorly penetrates ocular tissues. However, AMB is a drug of choice used for the treatment of fungal keratitis caused by Candida. Nonadecanoic acid (NDA) is a 19-carbon fatty acid obtained from plants or bacteria which has shown antifungal activity and acts as a fungal metabolite that can be used to potentiate the activity of AMB. AMB has shown a toxic effect at higher concentrations thus, a stable formulation consisting of both compounds showing antifungal action with lower AMB concentrations would reduce the risk of toxicity. The present study aims to formulate a stable formulation consisting of AMB and NDA in a nanostructured lipid carrier (NLC) system for the treatment of fungal keratitis. AMB-NLC and AMB-NDA-NLCs were prepared using a hot homogenizer and cold probe sonication method. These formulations were kept for stability at 4˚C, 25˚C, and 40˚C and were evaluated for physicochemical properties. Drug-loaded Pegylated (PEG) NLCs were prepared, sterilized using autoclaving and/or filtration, and evaluated for their physicochemical properties. The optimized NLC formulation showed particle size, polydispersity index, and zeta potential of 264.1±8.2 nm, 0.46±0.02, and -19.1±0.32 mV, respectively. Moreover, lead NLC dispersion showed an entrapment efficiency of 73.9±5.9%. Lead colloidal dispersion was stable for over a month under all conditions, and a steep decrease in Drug Content (DC) was seen in two months’ data. Antifungal efficacy study shows a 2-fold increase in the activity of AMB in the presence of NDA.
Recommended Citation
Shah, Vishal, "Design of an Ophthalmic Nanostructured Lipid Carrier Containing Amphotericin B and Nonadecanoic Acid for the Management of Fungal Keratitis" (2022). Electronic Theses and Dissertations. 2457.
https://egrove.olemiss.edu/etd/2457
Concentration/Emphasis
Pharmaceutical Science