Advisor(s)

Ban-An Khaw

Contributor(s)

Samuel Gatley, Carolyn W. Lee-Parsons

Date of Award

2010

Date Accepted

8-2010

Degree Grantor

Northeastern University

Degree Level

M.S.

Degree Name

Master of Science

Department or Academic Unit

Bouve College of Health Sciences. Department of Pharmaceutical Sciences

Keywords

health sciences, iron toxicity, human organs, heart, liver, mesylates, DFO

Subject Categories

Medical sciences, Deferoxamine, Liposomes

Disciplines

Pharmacy and Pharmaceutical Sciences

Abstract

The aim of this study was to prepare and characterize Deferoxamine mesylate (DFO) loaded liposomal formulations for targeted delivery to specific organs such as the liver and heart and also to increase the circulation time of DFO in the body for enhanced delivery for potential treatment of iron toxicity. Liposomes which have been extensively studied in the last few decades are spherical lipid vesicles having one or more phospholipid bilayers encapsulating an aqueous core containing the active drug. The preliminary study of this research focuses on optimization of the method for preparation of small unilamellar vesicles and physical characterization of six different DFO encapsulated liposomal formulations. Three different surface modifications of the liposomes employed in this research are grafting of a polyethylene glycol moiety on conventional liposomes to increase the blood circulation time of the encapsulated drug, addition of mannose moieties to the lipid bilayer to target the mannose receptors present on the Kupffer cells in the liver and use of DOTAP which is a cationic lipid to facilitate drug targeting to the heart and the liver via ionic interaction. Focus was also given to the characterization of size, surface charge and drug incorporation capacity of these liposomes. The final step in the proposed study was focused on in vitro and in vivo targeting of the mannosylated liposomes to the mannose receptors in the liver. As a part of this study the liposomes formulated with rhodamine labeled lipid were used for qualitative and quantitative experiments. The quantitative and qualitative studies were undertaken via FACS analysis and fluorescence microscopy respectively. Successful completion of this set of experiments confirm that Deferoxamine loaded mannosylated liposomes can be used to increase the accumulation of the drug in the kupffer cells of the liver and that cationic liposomes may suffice in targeting to hepatic cells in general.

Document Type

Master's Thesis

Rights Information

copyright 2010

Rights Holder

Parita Ghia


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