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A novel approach to targeted drug de...

Ji, Bingqing.

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A novel approach to targeted drug delivery for treatment of brain cancer.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	A novel approach to targeted drug delivery for treatment of brain cancer./
作者:	Ji, Bingqing.
面頁冊數:	150 p.
附註:	Director: D. Robert Lu.
Contained By:	Dissertation Abstracts International62-09B.
標題:	Health Sciences, Oncology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3025317
ISBN:	0493372024

A novel approach to targeted drug delivery for treatment of brain cancer.
Ji, Bingqing.

A novel approach to targeted drug delivery for treatment of brain cancer. - 150 p.

Director: D. Robert Lu.

Thesis (Ph.D.)--University of Georgia, 2001.

The main purpose of this study was to develop a new compound for use in boron neutron capture therapy (BNCT) that has following properties: (1) Carries boron-10. (2) Is actively accumulated by tumor cells. (3) Can be incorporated into low-density lipoprotein or other formulation that can function as a system of boron delivery selectively to tumor cells. We proposed and developed boronated cholesterol (cholesterol carborane conjugate, BCH), which (because it has structure and chemical properties similar to those of cholesteryl ester in the core of LDL) should be incorporated into the LDL core. Additionally, tumor cells with high LDL activity were expected to accumulate more of these LDL carriers of boron and thereby become targets of BNCT.

ISBN: 0493372024Subjects--Topical Terms:

1018566
Health Sciences, Oncology.

A novel approach to targeted drug delivery for treatment of brain cancer.
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245 1 0 $a A novel approach to targeted drug delivery for treatment of brain cancer.
300 $a 150 p.
500 $a Director: D. Robert Lu.
500 $a Source: Dissertation Abstracts International, Volume: 62-09, Section: B, page: 3983.
502 $a Thesis (Ph.D.)--University of Georgia, 2001.
520 $a The main purpose of this study was to develop a new compound for use in boron neutron capture therapy (BNCT) that has following properties: (1) Carries boron-10. (2) Is actively accumulated by tumor cells. (3) Can be incorporated into low-density lipoprotein or other formulation that can function as a system of boron delivery selectively to tumor cells. We proposed and developed boronated cholesterol (cholesterol carborane conjugate, BCH), which (because it has structure and chemical properties similar to those of cholesteryl ester in the core of LDL) should be incorporated into the LDL core. Additionally, tumor cells with high LDL activity were expected to accumulate more of these LDL carriers of boron and thereby become targets of BNCT.
520 $a The chemical reaction conditions for this new compound were determined and optimized. The structure of this compound consisted of one molecule of cholesterol covalently bound to one molecule of carborane, which was confirmed by elemental analysis, nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopy. Because the compound is extremely insoluble (estimated to be <1 ng/ml in aqueous solution and <2 μg/ml in commonly used pharmaceutical solvents, such as propylene glycol 400 and glycerin), formulating this compound was a great challenge.
520 $a BCH-liposomes were thus prepared and characterized. The preparation conditions were optimized to maximize encapsulation of the BCH. After a 16-h incubation, the cellular uptake of BCH-liposomes was about 3.3 times that of BCH in IPA solution. In addition, the 9L glioma cell uptake of BCH-liposomes and carborane-liposomes was almost the same.
520 $a The interaction between BCH-liposomes and LDL was demonstrated by agarose gel electrophoresis. The results showed that BCH was transferred from the liposomes to LDL after incubation of LDL with BCH liposome. In addition, intracerebral injection was tested in glioma rat model and it was found that BSH concentrated at a significantly higher level in tumor tissue (24.5 ± 4.7 μg/g tissue) than in normal brain tissue (0.67 ± 0.21 μg/g tissue).
520 $a In conclusion, a cholesterol-based boron-containing drug has been synthesized, which when formulated into liposomes or LDL, can serve as a selective carrier of boron to brain tumor cells. In addition, intracerebral injection of these formulations might further enhance tumor-specific deposition.
590 $a School code: 0077.
650 4 $a Health Sciences, Oncology. $3 1018566
650 4 $a Health Sciences, Pharmacy. $3 1017737
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710 2 0 $a University of Georgia. $3 515076
773 0 $t Dissertation Abstracts International $g 62-09B.
790 $a 0077
790 1 0 $a Lu, D. Robert, $e advisor
791 $a Ph.D.
792 $a 2001
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