Rationale drug delivery for cancer therapy : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
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[College Station, Tex.] :
[Texas A&M University System Health Science Center],
[2013]
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| Subjects: |
| Abstract: | ABSTRACT: Metastases and multidrug resistance (MDR) are obstacles against successful cancer therapy. Our objective is to design suitable drug delivery systems which can deliver anticancer drugs specifically to the cancer cells in sufficient concentration, for prolonged period of time, and avoid the toxic side-effects of anticancer drugs. In this study, we have developed two different drug delivery systems, namely polymeric mixed micelles and zirconium phosphate (ZrP) nanoplatelets (NPs) for delivery of several anticancer drugs to various cancers. Lack of selectivity, poor solubility, metabolic instability, and development of multidrug resistance are some of the major challenges in designing dosage regimens for administering chemotherapeutic agents to cancer patient. Polymeric micelles have been recognized as one of the most promising strategies to deliver poorly water soluble anticancer drugs in the past. We have chosen this system for delivery of chemotherapeutic agents such as gambogic acid, curcumin, and 17-AAG to various cancers. We hypothesized that incorporation of drugs into micelles can increase solubility, circulation time of the drug, and improvement of their anticancer effect in vitro and in vivo. In the present study, we have demonstrated that polymeric mixed micelles can encapsulate a large amount of anticancer drugs, sustain drug release, improves cellular internalization and cytotoxicity of the anticancer drugs in vitro and in vivo to various cancers. Metastatic cancer is a stage of cancer where the disease has spread to distant organs. Our approach is to use novel ZrP NPs, an inorganic layered nanoparticle for delivery of doxorubicin (DOX) to breast cancer cells and control release of drugs inside the cells. The proposed layered carrier can be prepared in the 50-200 nm size range with platelet-like shape. ZrP NPs alone are non-toxic to human cells, can intercalate a high load of DOX and sustain DOX release for more than 14 days. DOX:ZrP nano-platelets exhibited provides a higher uptake into breast cancer cells as compared to free doxorubicin. DOX loaded ZrP NP (DOX:ZrP) showed 50-fold higher toxicity to MCF-7 breast carcinoma cells and 3 fold higher cytotoxicity to MDA-MB-231 breast carcinoma cells compared with free doxorubicin. In summary, the results suggested that both polymeric mixed micelles and ZrP NPs systems can be used as a drug delivery system for cancer therapy especially for metastatic and multidrug resistant cancers. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the School of Graduate Studies of the Texas A&M University System Health Science Center in partial fulfillment of the requirements for the degree of Doctor of Philosophy May 2013." Approved as to style and content by: M. Delwar Hussain, Abraham Clearfield, Allison C. Rice-Ficht, Steve Maxwell, Van G. Wilson. |
| Physical Description: | xv, 174 leaves : illustrations (mostly color) ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 20-32, 59-65, 85-91, 109-114, 143-147, 156-160). |