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Sulfonamide based polymeric drug del...

Sethuraman, Vijay Anand.

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Sulfonamide based polymeric drug delivery systems for acidic solid tumors.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Sulfonamide based polymeric drug delivery systems for acidic solid tumors./
作者:	Sethuraman, Vijay Anand.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2008,
面頁冊數:	147 p.
附註:	Source: Dissertation Abstracts International, Volume: 69-01, Section: B, page: 3340.
Contained By:	Dissertation Abstracts International69-01B.
標題:	Pharmacy sciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3299740
ISBN:	9780549436621

Sulfonamide based polymeric drug delivery systems for acidic solid tumors.
Sethuraman, Vijay Anand.

Sulfonamide based polymeric drug delivery systems for acidic solid tumors. - Ann Arbor : ProQuest Dissertations & Theses, 2008 - 147 p.

Source: Dissertation Abstracts International, Volume: 69-01, Section: B, page: 3340.

Thesis (Ph.D.)--The University of Utah, 2008.

This dissertation focused on the design and evaluation of an innovative polymeric drug delivery system for acidic solid cancer tumors. A sulfonamide-based pH-sensitive polymer was developed to mask a conventional delivery system, such as a gene carrier or a polymeric micelle, during systemic circulation and unmask it at the acidic tumor.

ISBN: 9780549436621Subjects--Topical Terms:

3174369
Pharmacy sciences.

Sulfonamide based polymeric drug delivery systems for acidic solid tumors.
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245 1 0 $a Sulfonamide based polymeric drug delivery systems for acidic solid tumors.
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300 $a 147 p.
500 $a Source: Dissertation Abstracts International, Volume: 69-01, Section: B, page: 3340.
502 $a Thesis (Ph.D.)--The University of Utah, 2008.
520 $a This dissertation focused on the design and evaluation of an innovative polymeric drug delivery system for acidic solid cancer tumors. A sulfonamide-based pH-sensitive polymer was developed to mask a conventional delivery system, such as a gene carrier or a polymeric micelle, during systemic circulation and unmask it at the acidic tumor.
520 $a The pH-sensitive polymer, poly(methacryloyl sulfadimethoxine)- block-PEG (PSD-b-PEG) was synthesized and evaluated in a gene delivery model. Plasmid DNA was complexed with polyethyleneimine (PEI), which was further complexed with PSD-b-PEG to construct the gene delivery nanoparticle. The nanoparticles were 300 nm in size and showed low cytotoxicity (80%) and low transfection at pH 7.4 due to shielding of PEI by PSD-b-PEG and high cytotoxicity (20%) and high transfection at pH 6.6, indicating deshielding. This demonstrated that PSD- b-PEG was able to discern the small difference in pH between normal and tumor tissues.
520 $a Along the same principle, PSD-b-PEG was employed in a micelle system. The micelle was made of a poly(L-lactic acid) (PLLA) core and a polyethylene glycol (PEG) shell conjugated to TAT (TAT-micelle). The anionic PSD was complexed with cationic TAT to achieve the carrier (PMC). Flow cytometry and confocal microscopy showed significantly higher uptake of PMCs at pH 6.6 compared to pH 7.4 indicating shielding at normal pH and deshielding at tumor pH. In vivo evaluation of the DOX loaded PMCs in tumor bearing mice showed tumor regression up to 33 days compared to 12 days for unshielded TAT-micelles. Extravasation in the mice was visualized with a window chamber model. For PMCs the micelle extravasation was sustained up to 1 hr compared to TAT-micelles, which showed extravasation only up to 10 min.
520 $a After this, a new pH sensitive polymer, (poly(L-cystine bisamide- g-sulfadiazine))-b-PEG (PCBS-b-PEG), was synthesized. This polymer was not only able to mimic the PSD- b-PEG but also was biodegradable. In the presence of cysteine, PCBS degraded rapidly but was stable when complexed with PEI. An invitro cytotoxicity assay with PCBS-b-PEG complexed with DOX loaded TAT-micelles showed that the carrier was able to distinguish pHs 7.2 and 7.0.
590 $a School code: 0240.
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710 2 $a The University of Utah. $3 1017410
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793 $a English
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