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Dissertation-Pratima-02 10 2015 revised.pdf (5.05 MB)
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Functional Anchoring Lipids for Drug Delivery Carrier Fabrication and Cell Surface Re-Engineering Applications
Author Info
Vabbilisetty, Pratima
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=csu1424175323
Abstract Details
Year and Degree
2014, Doctor of Philosophy in Clinical-Bioanalytical Chemistry, Cleveland State University, College of Sciences and Health Professions.
Abstract
For decades, lipid vesicular bodies such as liposomes have been widely used and explored as biomimetic models of cell membranes and as drug/gene delivery carrier systems. Similarly, micellar iron oxide nanoparticles have also been investigated as potential MRI agents as well as drug delivery carrier systems. Cell surface carbohydrate-protein interactions allow them to serve as markers for recognition of many molecular and cellular activities thereby, are exploited as attractive molecules for surface modification of nanocarrier systems with purpose for tissues specific targeting and biocompatibility. In addition, the cell lipid membrane serves as an important platform for occurrence of many biological processes that are governed and guided by cell surface receptors. Introduction of chemoselective functional groups, via bio-orthogonal conjugation strategies, at the cell surface facilitates many cellular modifications and paves path for novel and potential biomedical applications. Anchoring lipids are needed for liposome surface functionalization with ligands of interest and play important roles in ligand grafting density, liposomes stability and biological activity. On the other hand, anchoring lipids are also needed for cell surface re-engineering by lipid fusion approach and have high impact for ligand insertion efficiency and biological activity. Overall, in this dissertation study, functional anchoring lipids for glyco-functionalized carrier systems and for efficient cell surface re-engineering applications were systematically investigated, respectively. Firstly, investigation of the synthesis of glyco-functionalized liposome systems based on phosphatidylethonalamine (PE) and cholesterol (Chol) anchoring lipids, prepared by post chemically selective functionalization via Staudinger ligation were carried out. The effect of anchor lipids on the stability, encapsulation and releasing capacity of the glycosylated liposomes were investigated by dynamic light scattering (DLS) technique and by entrapping 5, 6-carboxyfluorescein (CF) dye and monitoring the fluorescence leakage, respectively. Overall, the Chol-anchored liposomes showed faster releasing rate than DSPE-anchored liposomes. This could be due to the increase in rigidity of the lipid membrane upon inclusion of Chol, thereby, leading to fast leakage of liposomes. Second, the potential effects of phospholipid (PE) and cholesterol (Chol)-based anchor lipids on cell surface re-engineering via copper free click chemistry were assessed with RAW 264.7 cells as model. The confocal microscopy and flow cytometry results indicated the successful incorporation of biotinylated Chol-based anchor lipids after specific streptavidin-FITC binding onto the cell surface. Higher fluorescence intensities from the cell membrane were observed for Chol-based anchor lipids when compared to DSPE as anchoring lipid. Furthermore, cytotoxicity of the synthesized biotinylated anchor lipids on the RAW 264.7 cells was assessed by MTT assay. The MTT assay results further confirmed that cell surface re-engineering via lipid anchoring approach strategy has very little or negligible amount of cytotoxicity on the cell viability. Thus, this study suggests the possible use of these lipids for potential cell surface re-engineering applications. In addition, synthesis of lipid coated iron oxide nanoparticles via dual solvent exchange approach and their glyco-functionalization via Staudinger ligation were investigated and characterized by FT-IR and TEM techniques. The stability of iron oxide nanoparticles with varying compositions of lipid anchors was evaluated by dynamic light scattering technique.
Committee
Xue-Long Sun, Ph.D. (Committee Chair)
Aimin Zhou, Ph.D. (Committee Member)
Bin Su, Ph.D. (Committee Member)
John Turner II, Ph.D. (Committee Member)
Petru Fodor, Ph.D. (Committee Member)
Pages
209 p.
Subject Headings
Chemistry
Keywords
Liposomes, Nanoparticles, Cell Surface Re-engineering, Lipids, Click Chemistry, Staudinger Ligation
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Citations
Vabbilisetty, P. (2014).
Functional Anchoring Lipids for Drug Delivery Carrier Fabrication and Cell Surface Re-Engineering Applications
[Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1424175323
APA Style (7th edition)
Vabbilisetty, Pratima.
Functional Anchoring Lipids for Drug Delivery Carrier Fabrication and Cell Surface Re-Engineering Applications.
2014. Cleveland State University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=csu1424175323.
MLA Style (8th edition)
Vabbilisetty, Pratima. "Functional Anchoring Lipids for Drug Delivery Carrier Fabrication and Cell Surface Re-Engineering Applications." Doctoral dissertation, Cleveland State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=csu1424175323
Chicago Manual of Style (17th edition)
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Document number:
csu1424175323
Download Count:
583
Copyright Info
© 2014, some rights reserved.
Functional Anchoring Lipids for Drug Delivery Carrier Fabrication and Cell Surface Re-Engineering Applications by Pratima Vabbilisetty is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Cleveland State University and OhioLINK.