Graduation Year

2019

Document Type

Thesis

Degree

M.S.

Degree Name

Master of Science (M.S.)

Degree Granting Department

Dean's Office

Major Professor

Vijaykumar Sutariya, M.Pharm, Ph.D.

Committee Member

Yashwant Pathak, M.Pharm, Ph.D.

Committee Member

Pranav Patel, Ph.D.

Keywords

AMD, Pazopanib, PLGA nanoparticles, sustained release

Abstract

Age-related macular degeneration (AMD) is a reason of severe vision loss worldwide. Pazopanib is a multitargeted tyrosine kinase inhibitor drug that can reduce neovascularization by mainly acting on vascular endothelial growth factor receptor (VEGFR). An intraocular injection to posterior segment of eye of anti-VEGF agent at present represents the cornerstone of therapies for AMD. However, challenges in targeting and delivering drug to eye’s posterior segment well as difficulties arising from repetitive frequent intraocular injections, which requires novel drug delivery method. In this study, pazopanib loaded PLGA‐NPs were prepared and the studied formulation had particle size of 132.1 ± 1.4 nm with PDI of 0.125 ±0.023 and 0.004± 0.13 mV for zeta potential. Entrapment efficiency was found 33.9 ± 2.5%. In vitro drug release study showed sustained drug lease. In vitro characterization in human retinal pigmented epithelial cell line described MTT assay, cellular uptake, wound scratch and anti-VEGF assay, which indicated that nanoparticles formulation had less toxicity, higher uptake, had superior anti-angiogenic potential and showed prolonged inhibition of VEGF activity. Therefore, pazopanib loaded PLGA nanoparticles were successfully developed, characterized and demonstrated its treatment of AMD.

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