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Colon-targeted delivery of 9-aminoca...

The University of Utah.

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Colon-targeted delivery of 9-aminocamptothecin by HPMA copolymer conjugates for the treatment of colon cancer.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Colon-targeted delivery of 9-aminocamptothecin by HPMA copolymer conjugates for the treatment of colon cancer./
作者:	Gao, Songqi.
面頁冊數:	186 p.
附註:	Source: Dissertation Abstracts International, Volume: 70-01, Section: B, page: 0309.
Contained By:	Dissertation Abstracts International70-01B.
標題:	Chemistry, Pharmaceutical. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3342895
ISBN:	9780549977308

Colon-targeted delivery of 9-aminocamptothecin by HPMA copolymer conjugates for the treatment of colon cancer.
Gao, Songqi.

Colon-targeted delivery of 9-aminocamptothecin by HPMA copolymer conjugates for the treatment of colon cancer. - 186 p.

Source: Dissertation Abstracts International, Volume: 70-01, Section: B, page: 0309.

Thesis (Ph.D.)--The University of Utah, 2009.

As a consequence of the colon-specific release of unmodified 9-AC from the polymer conjugates, antitumor efficacy can be anticipated in future clinical studies for the treatment of colon cancer.

ISBN: 9780549977308Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

Colon-targeted delivery of 9-aminocamptothecin by HPMA copolymer conjugates for the treatment of colon cancer.
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245 1 0 $a Colon-targeted delivery of 9-aminocamptothecin by HPMA copolymer conjugates for the treatment of colon cancer.
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500 $a Source: Dissertation Abstracts International, Volume: 70-01, Section: B, page: 0309.
502 $a Thesis (Ph.D.)--The University of Utah, 2009.
520 $a As a consequence of the colon-specific release of unmodified 9-AC from the polymer conjugates, antitumor efficacy can be anticipated in future clinical studies for the treatment of colon cancer.
520 $a Due to nonspecific-toxicity, cancer treatment with 9-aminocamptothecin (9-AC) caused severe side effects, and failed to show any meaningful clinical activity. The development of macromolecular drug-delivery systems is a potent strategy to enhance therapeutic efficiency and minimize systemic toxicity by target-selective delivery of toxic anticancer drugs. In this research, water soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-9-AC conjugates were designed, synthesized and evaluated for oral colon-specific delivery of 9-AC for the treatment of colon cancer.
520 $a The specific objectives of this project were achieved by four steps. In the first HPMA copolymer-9-AC conjugate for oral colon-specific drug delivery was designed, synthesized, and characterized. The design of the spacer ensured a fast and highly efficient release of unmodified 9-AC from the polymer in the colon by azo bond cleavage followed by an 1,6-elimination reaction. An in vitro degradation study indicated that this conjugate was stable in simulated upper GI tract conditions. In the second step, comparative studies between the polymer conjugate and free drug have been performed to assess their biodistribution and pharmacokinetics in mice. Colon-specific release of 9-AC from the polymer conjugates produced high local-regional drug concentrations. The high and sharp plasma drug concentration profiles from free drug were in contrast to the relatively low and flat pharmacokinetic profiles obtained from drug released from the HPMA copolymers. In the third step, a pharmacokinetic model was developed to quantitate and predict colon-specific drug release from the polymer conjugate and its absorption behavior after oral administration in rats. This model delineated the impact of GI transit, drug absorption rate, and first-pass metabolism on drug disposition. In the fourth step, anticancer efficacy of the colon-specific drug delivery by the polymer conjugates was assessed in nude mice bearing both orthotopic and subcutaneous human colon carcinoma xenografts. It was found that colon-specific release of unmodified 9-AC from HPMA copolymer conjugates enhanced antitumor activity and minimized systemic toxicity compared to free drug treatment in two colon tumor models.
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