Author Type

Graduate Student

Date of Award

2007

Document Type

Dissertation

Publication Status

Version of Record

Submission Date

October 2026

Thesis/Dissertation Advisor [Chair]

Fields, Gregg B.

Abstract

Liposomes of varying lipid compositions are currently used as drug carriers. and great efforts have been made to target these vehicles to specific cellular receptors. Previous targeting components include peptides. proteins. antibodies. or vitamins. CD44/CSPG is among the receptors overexpressed in metastatic melanoma. and the sequence to which it binds within the type IV collagen triple-helix has been identified. A triple-helical '·peptide-amphiphile .. (al(JV)1263-1277 PA) which binds CD44/CSPG has been constructed and incorporated into liposomes of differing lipid compositions. Liposomes containing distearoyl phosphatidylcholine (DSPC) as the major bilayer component. in combination with distearoyl phosphatidylglycerol (DSPG) and cholesterol. were more stable than analogous liposomes containing dipalmitoyl phosphatidylcholine (DPPC) instead of DSPC. The presence of the al(JV)1263-1277 PA conferred greater stability to the DPPC liposomal systems. and did not affect the stability of the DSPC liposomes. The addition of either PEG 750 or PEG 2000 (5 mol %) to DSPG/DSPC/Chol liposomes did not affect the stability of this system. Fluorophore delivery of rhodamine loaded liposomes to cells varymg 111 CD44/CSPG expresston was determined usmg fluorescence microscopy. The CD44/CSPG receptor content for two normal fibroblast cell lines, BJ and Hs895Sk, and a highly metastatic melanoma derived cell line, M 14#5. was determined using whole cell ELISA. The results of the ELISA showed varying levels of CD44 receptors amongst the cell lines. with M 14#5 cells having the most. A positive correlation was observed for cellular fluorophore delivery by the ai(IV)1263-1277 PA liposomes and CD44/CSPG receptor content. Conversely, non-targeted liposomes delivered minimal fluorophore to cells regardless of the CD44/CSPG receptor content. When cells were treated with exogeneous a I (IV) 1263-1277, prior to incubation with a I (IV) 1263 -1277 PA liposomes, a dose-dependent decrease in the amount of fluorophore delivered was observed with respect to increasing concentrations of exogeneous al(IV)1263-1277. In addition, we have found a positive correlation between the cytotoxic effect of ai(IV)l263-1277 PA targeted liposomes (with and without PEG) loaded with doxorubicin and the CD44/CSPG content amongst the three different cell lines. This trend was not observed with non-targeted liposomes. These findings provide the possibility of a novel drug carrier system to be used in future clinical applications against metastatic melanoma.

Extent

159 p.

Comments

Includes bibliography.|Dissertation (Ph.D.)--Florida Atlantic University, 2007.|FAU Electronic Theses and Dissertations Collection|Charles E. Schmidt College of Science|Includes bibliography.

Identifier

FA00000866

Format

pdf

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