Electronic Theses and Dissertations

Date of Award

1-1-2020

Document Type

Thesis

Degree Name

M.S. in Pharmaceutical Science

First Advisor

Chalet Tan

Second Advisor

Jason Paris

Third Advisor

Walter Chambliss

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

The blood-brain barrier (BBB), formed by the endothelial cells of the brain capillaries, inhibits the penetration of many therapeutic compounds into the brain. Liposomes, which have unique physicochemical characteristics, have been widely investigated for the drug delivery system across BBB. In the current study, FITC-dextran was used as a model drug that encapsulated in a liposomal formulation to investigated its ability to overcome the blood-brain barrier for targeted brain delivery of therapeutic agents. Here, non-targeted liposome (NT LPs) and RVG-modified liposome (RVG LPs) were prepared. The NT LPs and RVG LPs were about 97 and 101 nm in diameter with the zeta potential of -27.0 mV and -21.2 mV, respectively. In vitro study in mouse SH-SY5Y neuroblastoma cells and mixed glial cells demonstrated that the RVG LPs were taken up with enhanced efficiency comparing to the NT LPs. In vitro release study results indicated the sustained release of FITC-dextran from NT LPs. A preliminary pharmacokinetic study showed prolonged circulation time of FITC-dextran encapsulated in NT LPs compared to the free form. As expected, free FITC-dextran manifested no brain distribution. Further studies on the pharmacokinetics of RVG LPs are warranted, to establish the proof of concept for its application in brain-targeted drug delivery.

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