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Synthesis and Characterization of Hybrid Co-Delivery Nanoparticles for Triple Negative Breast Cancer Treatment

Kennell, Carly M
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470741290

Abstract Details

2016, MS, University of Cincinnati, Engineering and Applied Science: Chemical Engineering.
The work in this document describes the synthesis, optimization, characterization, and performance of a nanoparticle drug delivery system. The application of this system is Triple Negative Breast Cancer (TNBC), but may be applied to other situations. TNBC is a very aggressive form of cancer that is susceptible to metastasis and rapid tumor growth. It also does not overexpress any common biomarkers, making it difficult to treat. The drug delivery systems consist of nanoparticles (NP(s)) utilizing biocompatible polymers, calcium phosphate (CaP), and lipids to deliver two types of therapeutic entities. One of these is a hydrophobic chemotherapy drug, paclitaxel (pac), and the other is a hydrophilic gene therapy microRNA inhibitor (miRi). Pac is a common chemotherapeutic drug that is used to kill many types of cancerous cells. Unfortunately, this drug cannot differentiate between healthy and cancerous cells; so healthy cells are compromised during the treatment. Also, the cancerous cells may develop drug resistance to pac, resulting in more drug needed to kill the same amount of cells, thus more side effects for the patient. Fortunately, these delivery systems combine chemotherapy with gene therapy. Gene therapy is a type of treatment for cancers that sends inhibitors or promoters to overexpressed RNA or DNA that are involved in tumor growth and metastases. Here, a miRi for the overexpressed microRNAs 221 and 222 is used for gene therapy. By delivering the inhibitor, drug resistance is suppressed and the cancerous cells are less susceptible to metastases and tumor growth. By strategically combining these two therapeutic entities, three architectures have been disclosed in this work. Two of these three architectures are capable of effectively encapsulating both entities and killing the cancerous cells while using less pac. The other architecture is capable of a very sound structure as well as encapsulating miRi. However, the pac is susceptible to leaching and therefore the results are not repeatable and not sound for this combination of chemotherapy drug and miRi. The architecture may work with a different chemotherapeutic drug. The first structure disclosed encapsulates both entities in the core of the NP. To encapsulate both of these displaying different physiochemical properties, lipid coated CaP cores were used to coprecipitate with miRi and were further encapsulated along with pac. CaP exists as a precipitate in neutral conditions, or biological pH, and dissolves at acidic conditions, or intracellular pH. In this structure, the pac is released first, followed by the pH sensitive release of miRi. Ideally, the miRi should be released first to pretreat the cells and minimize drug resistance. Then the pac should release to kill the non-resistant cells. This idea leads to the second and third structures. These structures utilize a CaP shell on the outside of the particle. The pac is encapsulated inside the core and the miRi is coprecipitated with the CaP in the shell. Thus, when the pH is low, such as an intracellular environment, the CaP will dissolve, releasing the miRi. Then after the reinforcing shell has solubilized, the pac will exhibit a sustained release.
Joo Youp Lee, Ph.D. (Committee Chair)
Yoonjee Park, Ph.D. (Committee Member)
Jing-Huei Lee, Ph.D. (Committee Member)
98 p.
Chemical Engineering
drug delivery; nanoparticle; calcium phosphate; codelivery; breast cancer

Recommended Citations

Citations

  • Kennell, C. M. (2016). Synthesis and Characterization of Hybrid Co-Delivery Nanoparticles for Triple Negative Breast Cancer Treatment [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470741290

    APA Style (7th edition)

  • Kennell, Carly. Synthesis and Characterization of Hybrid Co-Delivery Nanoparticles for Triple Negative Breast Cancer Treatment. 2016. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470741290.

    MLA Style (8th edition)

  • Kennell, Carly. "Synthesis and Characterization of Hybrid Co-Delivery Nanoparticles for Triple Negative Breast Cancer Treatment." Master's thesis, University of Cincinnati, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470741290

    Chicago Manual of Style (17th edition)

ucin1470741290
396
© 2016, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.