Cancer is currently the second most common cause of death in the world. Despite tremendous progress in the treatment of different forms of cancer, the five year survival rates for lung, colorectal, breast, prostate, pancreatic and ovarian cancers remain quite low. New therapies are urgently needed for the better management of these diseases. In this context, both therapeutic gene and drug delivery constitute promising approaches for cancer treatment and are addressed in this thesis. Focusing on gene delivery, we are proposing the use new pyridinium amphiphiles for obtaining gene delivery systems with improved stability and efficiency and low toxicity (Chapters 2 and 3). The main focus was on pyridinium gemini surfactants (GSs), which possess a soft charge, a high charge/mass ratio and a high molecular flexibility - all key parameters that recommend their use in synthetic gene delivery systems with in vitro and in vivo efficiency. In Chapter 2, we optimized a novel DNA delivery systems through interfacial engineering of pyridinium GS at the level of linker, hydrophobic chains and counterions. In Chapter 3, we tested the effects of blending pyridinium cationic GS into pyridinium cationic lipid bilayers and we have evaluated these blends towards plasmid DNA compaction and delivery process. We have also correlated the cationic bilayer composition with the dynamics of the DNA compaction process, and with transfection efficiency, cytotoxicity and internalization mechanism of resulted nucleic acid complexes. Toward improved drug delivery systems, we introduced new amphiphilic block copolymers synthesized from biocompatible and biodegradable segments. Although their capabilites for loading, transport and release of lipophilic substances stored in their hydrophobic cores are widely known, their stability in vivo is limited due to rapid degradation by esterases present in the body. In Chapter 4, we examined the possibility to increase the enzymatic stability of PEG-PCL macromolecular amphiphiles through interfacial engineering, in a process which separates the hydrophilic/hydrophobic interface from the degradable/non-degradable block interface. We evaluated the stability, toxicity, drug loading and release properties of these new polymers using docetaxel as a model chemotherapeutic drug. The results revealed how hydrophilic/ hydrophobic interface tuning can be used to adjust key properties of polymeric drug delivery systems of this type. / Pharmaceutical Sciences
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/3558 |
| Date | January 2014 |
| Creators | Sharma, Vishnu Dutt |
| Contributors | Ilies, Marc A., Canney, Daniel J., Borenstein, Michael R., Fassihi, Reza, Wunder, Stephanie L. |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 218 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/3540, Theses and Dissertations |
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