Sonali Gupta

Date of Award

2013

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Colladay, Donald

Keywords

Liposomes, Drug Delivery, Membranes

Area of Concentration

Biophysics

Abstract

Liposomes, or membranous vesicles, with a radius less than 100 nm are called Small Unilamellar Vesicles (SULVs). The formation of stable SULVs is problematic since tension in the membrane due to its high curvature destabilizes the particles. In this study the spontaneous formation of SULVs was observed through two separate pathways, both involving structural precursors. SULVs formed through the bicellar phase have disk-like precursors whose morphology is dictated by the molar ratio of long and short chain phospholipids in solution. Here DMPC and DHPC were used in a 3.2:1 ratio to create SULVs of 34.3 +/- 0.24 nm at a concentration of 0.75% lipid w/v and 35.6 +/- 0.45 nm at a concentration of 1.0% lipid w/v. Ellipsoidal precursors yielded liposomes ranging from approximately 58 to 66 nm in radius, at highly dilute concentrations (0.03 to 0.09 % lipid w/v) indicating that at low concentrations the molar ratio of phospholipids incorporated within the structures shifts from the ideal input ratio. Lamellar sheets were not shown to result in SULVs, but may have malleability at threshold concentrations where the lamellae are undergoing unbinding transitions. The dynamics of disk growth hints at a mechanism by which the metastable morphologies of SULVs with structural precursors are maintained for longer periods than SULVs created through high-energy methods such as sonication. These vesicles were created for the purpose of optimizing anti-tumor drugs to glioblastoma multiforme cells through the enhanced permeability and retention effect. SULVs were found to diffuse through uniform porous media at rates 50 times faster than those of LULVs (Large Unilamellar Vesicles), indicating that they may be able to penetrate tumors to a greater extent than LULVs, which are also hindered by lower circulation half-lives. A study of size dependent leakage rates of encapsulated agents remained inconclusive. Overall, stable SULVs suitable for use in targeted drug delivery were successfully created and show promise for biological applications that require penetration of semi-permeable membranes, tissues, or vasculatures.

Rights

This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.

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