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NANOCARRIERS FOR THERAPEUTIC NUCLEIC ACID DELIVERY

Zhou, Chenguang
http://rave.ohiolink.edu/etdc/view?acc_num=osu1336584204

Abstract Details

2012, Doctor of Philosophy, Ohio State University, Pharmacy.
The objective of this dissertation research is to develop nanocarrier (NC) systems for therapeutic nucleic acid delivery and to investigate the mechanism and kinetics of cellular uptake and intracellular trafficking. Novel delivery systems consisting of cationic lipid, surfactant, calcium phosphate, and/or polymers were synthesized and evaluated for in vitro nucleic acid delivery efficiency. Chapters 2 contributes scientifically to the gene delivery field, with development of lipid-coated nano-calcium-phosphate (LNCP). Chapter 3 contributes to the field of siRNA delivery, with development of novel surfactant vesicles, SPANosomes (SPs), that can mediate efficient siRNA delivery in vitro. Chapter 4 is an extension of Chapter 3. The effects of formulation factors (SPANosome vs. cationic liposome) on siRNA delivery are studied from the mechanistic perspective. Chapter 3 and 4 together discover that helper components, Span 80 and DOPE, have a profound impact on the endocytic pathways of NCs, which leads to distinct the cellular pharmacokinetics and pharmacodynamics of siRNA delivered by different formulations. Chapter 5 demonstrates that polyamidoamine (PAMAM) dendrimers with a pentaerythritol derivative core can be used as carriers for siRNA. The PAMAM/siRNA complexes are shown to remain effective in the gene silencing in the presence of FBS, suggesting its potential as vectors for in vivo siRNA delivery. Future biological evaluation of the novel NCs in the present research is needed to understand the systemic PK and biodistribution properties of the NC/siRNA complexes. These results will form the basis for designing and conducting the preclinical pharmacological studies that demonstrate the therapeutic activities of nucleic acid drug in vivo.
Robert J. Lee, PhD (Advisor)
L. James Lee, PhD (Advisor)
Mitch A. Phelps, PhD (Committee Member)
Pharmaceuticals
nanoparticles; gene therapy; drug delivery; pharmacokinetics; siRNA; molecular beacon; intracellular trafficking

Recommended Citations

Citations

  • Zhou, C. (2012). NANOCARRIERS FOR THERAPEUTIC NUCLEIC ACID DELIVERY [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1336584204

    APA Style (7th edition)

  • Zhou, Chenguang. NANOCARRIERS FOR THERAPEUTIC NUCLEIC ACID DELIVERY. 2012. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1336584204.

    MLA Style (8th edition)

  • Zhou, Chenguang. "NANOCARRIERS FOR THERAPEUTIC NUCLEIC ACID DELIVERY." Doctoral dissertation, Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1336584204

    Chicago Manual of Style (17th edition)

osu1336584204
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© 2012, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.