Graduation Year

2020

Document Type

Thesis

Degree

M.S.M.S.

Degree Name

MS in Medical Sciences (M.S.M.S.)

Degree Granting Department

Graduate School

Major Professor

Vijaykumar Sutariya, Ph.D.

Committee Member

Manas Biswal, MFSc, Ph.D.

Committee Member

Pranav Patel, Ph.D.

Keywords

Anti-HIF agent, Anti-VEGF agent, Choroidal Neo-vascularization, Sustained release

Abstract

Age related Macular Degeneration (AMD), a multi-factorial age-related retinal hypoxic disorder resulting in irreversible loss of vision is the foremost cause of blindness in United States. Current treatment strategies used to treat disease involve multiple intraocular injections of Anti – VEGF agents into the vitreous of eye. In addition to the issues of drug localization and targeted delivery, the need to frequently inject drug into the eye raise patient compliance issues. These challenges call for sustained drug delivery system. In this study, a sustained drug delivery system was prepared by loading an anti- HIF agent, honokiol into MPEG-PCL polymer. These HON-MPEG-PCL micelles were characterized by measuring Size, PDI & zeta potential. In-vitro drug release study was conducted. DSC was performed to confirm entrapment of a drug in micelles. Micelles formed had a particle size of 30.8±0.8 nm with the PDI of 0.19 ± 0.0004 and Zeta potential was calculated to be -5.46 ±0.49 mv. Entrapment efficiency was calculated to be 64±0.135 %. In vitro drug release showed sustained release of formulation that reduces the need of frequent injections. Cell line studies for in-vitro characterization were conducted in human epithelial retinal cells (ARPE). Result from Cytotoxicity showed the formulation to be less toxic as compare to drug solution. Furthermore, ELISA studies performed showed the periodic downregulation of HIF and VEGF which are involved in underlying mechanism of AMD. Therefore, Honokiol-Loaded MPEG-PCL micelles were successfully developed and characterized. Cell line studies further showed the formulation to be effective in treatment of AMD.

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