Graduation Year

2020

Document Type

Thesis

Degree

M.S.

Degree Name

Master of Science (M.S.)

Degree Granting Department

Dean's Office

Major Professor

Yashwant V. Pathak, Ph.D.

Committee Member

Vijaykumar Sutariya, Ph.D.

Committee Member

Daniel J. Denmark, Ph.D.

Keywords

Nephrotoxicity, Cyclosporine A, PLGA nanoparticles

Abstract

Cyclosporine (CsA) is one of the main immune-suppressant agents which has been used widely in organ transplantation against graft rejection. However, the low oral bioavailability and the associated adverse effects such as nephrotoxicity are the main drawbacks of current usage of this drug. Thus, purpose of this research is to formulate PLGA nanoparticles of CsA to improve its effectiveness and to reduce the nephrotoxicity induced by the plain drug. CsA-loaded PLGA nanoparticles were prepared by the nanoprecipitation method. Particle size and zeta potential of the formulation was determined and percent drug entrapment were also determined. Quantitative estimation was carried out using validated UV spectroscopic method. The morphology of the nanoparticles was determined by Transmission Electron Microscopy. In vitro drug release profile was carried out utilizing dialysis method. In vitro cytotoxicity using MTT assay and in vivo toxicity studies are in progress and will be shared in the next presentations. The developed CsA loaded PLGA were developed and optimized having size around 80 nm with less than 0.2 PDI that shows narrow size distribution. The result from TEM studies also was in similar with DLS results. Zeta potential was found to be -29.32±2.7 mV, describing the stability of formulation. The optimized formulation could entrap 47.4±3.2 % of Cy-A in PLGA NPs. In vitro cytotoxicity using MTT assay shows fewer toxic effects in HEK-293 cells. CsA loaded PLGA nanoparticles were successfully developed and characterized. The size of the particles was in the nanometer range with narrow size distribution. This nanoformulations may serve as an alternative formulation for CsA for effective drug delivery and to reduce the side effects.

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