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Mechanisms of intestinal microsphere...

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Mechanisms of intestinal microsphere uptake and quantitative analysis of organ distribution for applications of oral drug delivery.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Mechanisms of intestinal microsphere uptake and quantitative analysis of organ distribution for applications of oral drug delivery./
Author:	Reineke, Joshua James.
Description:	241 p.
Notes:	Source: Dissertation Abstracts International, Volume: 69-11, Section: B, page: 6493.
Contained By:	Dissertation Abstracts International69-11B.
Subject:	Biology, General. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3335689
ISBN:	9780549898092

Mechanisms of intestinal microsphere uptake and quantitative analysis of organ distribution for applications of oral drug delivery.
Reineke, Joshua James.

Mechanisms of intestinal microsphere uptake and quantitative analysis of organ distribution for applications of oral drug delivery. - 241 p.

Source: Dissertation Abstracts International, Volume: 69-11, Section: B, page: 6493.

Thesis (Ph.D.)--Brown University, 2008.

Oral absorption of many potential pharmaceuticals is limited due to problems of enzyme degradation, dissolution and permeation. Bioadhesive poly(fumaric-co-sebacic) anhydride microspheres have been investigated as a promising solution to increase oral bioavailability of such pharmaceuticals by way of protection from the gastro-intestinal environment, increased resident time and enhanced internalization. Little research has been done in the past to understand the cellular mechanisms of microsphere internalization, particularly in the absorptive intestinal epithelium, and the resulting organ fate. Utilizing an in vivo isolated loop technique, quantitative tissue analysis and mechanism-specific uptake inhibition, the cellular mechanisms of microsphere uptake, uptake kinetics and organ distribution were studied. Pharmacokinetic studies indicated an improvement in oral bioavailability with small (<2 mum), bioadhesive microspheres, and was corroborated by evidence of increased uptake of bioadhesive microspheres in quantitative studies. Uptake and organ distribution were found to be dependant on microsphere size, microsphere chemistry, intestinal region of uptake and cellular uptake mechanism. Clathrin-mediated endocytosis was found to be the predominant mechanism of microsphere uptake in both the rat jejunum and ileum. The results potentiate the use of bioadhesive microspheres for increased oral bioavailability and organ directed therapies.

ISBN: 9780549898092Subjects--Topical Terms:

1018625
Biology, General.

Mechanisms of intestinal microsphere uptake and quantitative analysis of organ distribution for applications of oral drug delivery.
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008 100709s2008 ||||||||||||||||| ||eng d
020 $a 9780549898092
035 $a (UMI)AAI3335689
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100 1 $a Reineke, Joshua James. $3 1023367
245 1 0 $a Mechanisms of intestinal microsphere uptake and quantitative analysis of organ distribution for applications of oral drug delivery.
300 $a 241 p.
500 $a Source: Dissertation Abstracts International, Volume: 69-11, Section: B, page: 6493.
502 $a Thesis (Ph.D.)--Brown University, 2008.
520 $a Oral absorption of many potential pharmaceuticals is limited due to problems of enzyme degradation, dissolution and permeation. Bioadhesive poly(fumaric-co-sebacic) anhydride microspheres have been investigated as a promising solution to increase oral bioavailability of such pharmaceuticals by way of protection from the gastro-intestinal environment, increased resident time and enhanced internalization. Little research has been done in the past to understand the cellular mechanisms of microsphere internalization, particularly in the absorptive intestinal epithelium, and the resulting organ fate. Utilizing an in vivo isolated loop technique, quantitative tissue analysis and mechanism-specific uptake inhibition, the cellular mechanisms of microsphere uptake, uptake kinetics and organ distribution were studied. Pharmacokinetic studies indicated an improvement in oral bioavailability with small (<2 mum), bioadhesive microspheres, and was corroborated by evidence of increased uptake of bioadhesive microspheres in quantitative studies. Uptake and organ distribution were found to be dependant on microsphere size, microsphere chemistry, intestinal region of uptake and cellular uptake mechanism. Clathrin-mediated endocytosis was found to be the predominant mechanism of microsphere uptake in both the rat jejunum and ileum. The results potentiate the use of bioadhesive microspheres for increased oral bioavailability and organ directed therapies.
590 $a School code: 0024.
650 4 $a Biology, General. $3 1018625
650 4 $a Engineering, Biomedical. $3 1017684
650 4 $a Health Sciences, Pharmacology. $3 1017717
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710 2 $a Brown University. $3 766761
773 0 $t Dissertation Abstracts International $g 69-11B.
790 $a 0024
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3335689