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Effect of drug charge type, charge density, and molecular weight on corneal transport.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Effect of drug charge type, charge density, and molecular weight on corneal transport./
Author:	Liaw, Jiahorng.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 1992,
Description:	192 p.
Notes:	Source: Dissertations Abstracts International, Volume: 54-04, Section: B.
Contained By:	Dissertations Abstracts International54-04B.
Subject:	Pharmaceuticals. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9221491
ISBN:	9798208721759

Effect of drug charge type, charge density, and molecular weight on corneal transport.
Liaw, Jiahorng.

Effect of drug charge type, charge density, and molecular weight on corneal transport. - Ann Arbor : ProQuest Dissertations & Theses, 1992 - 192 p.

Source: Dissertations Abstracts International, Volume: 54-04, Section: B.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 1992.

This item must not be sold to any third party vendors.

Two major aspects of corneal absorption, namely membrane charge-size selectivity and the promoting effect of some penetration enhancers, were investigated. Studies on membrane charge selectivity involve: (a) testing the existence and significance of the permselectivity barrier on corneal transport of amino acids, and (b) determining the effect of charge type and charge density of amino acids on their absorption. To study the amino acid's charge type and density selectivity, two model amino acids, differing in charge but of similar size, were radioactively labelled and their movements across the cornea were determined with side-by-side diffusion cells. Results from these studies indicate that at physiological pH and pH above the isoelectric point (3.2), the cornea behaves as if it is negatively charged and is thus relatively less permeable to L-glutamic acid (pH 7 and 10) and functions as an ion-exchange membrane for L-lysine (pH 7 and 10). Below the isoelectric point, functional groups become protonated so that the cornea possesses a net positive charge and has the reverse effect on the permeation of L-glutamic acid. However, at low pH, lysine may have a specific effect on the corneal transport mechanism. Utilizing a broad range of hydrophilic polyethylene glycols (PEGs) and electron microscopic studies, the molecular weight dependence of corneal transport and the promoting mechanisms of penetration enhancers, were investigated. Absorption across corneal tissues exhibits a dependence on the molecular weight of PEGs and the molecular weight cutoff is between PEG 400 and PEG 600. Each penetration enhancer was found to affect the cornea and its permeability in a unique manner. Sodium deoxycholate appeared to have little effect on tissue morphology and does not significantly alter the molecular weight permeability profile of the cornea. In contrast, 1 mM digitonin caused severe alteration of the corneal epithelium and also greatly increased the absorption of PEGs. Selective molecular weight effects were seen with 1 mM cytochalasin B and the absorption of the PEG 400 and PEG 600 oligomers increased similar to that of PEG 200. However, the degree of absorption of PEG 1000 did not appear to change over a 4 hour perfusion period. Correlation of mucosal integrity with the effectiveness of cytochalasin B indicates that this agent indeed acts on the tight junction by opening intercellular spaces. The effect of EDTA on the corneal transport of PEG did not significantly affect the molecular weight permeability profile and it may involve some intracellular messengers.

ISBN: 9798208721759Subjects--Topical Terms:

3562593
Pharmaceuticals.

Effect of drug charge type, charge density, and molecular weight on corneal transport.
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100 1 $a Liaw, Jiahorng. $3 3680588
245 1 0 $a Effect of drug charge type, charge density, and molecular weight on corneal transport.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 1992
300 $a 192 p.
500 $a Source: Dissertations Abstracts International, Volume: 54-04, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Robinson, Joseph R.
502 $a Thesis (Ph.D.)--The University of Wisconsin - Madison, 1992.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a Two major aspects of corneal absorption, namely membrane charge-size selectivity and the promoting effect of some penetration enhancers, were investigated. Studies on membrane charge selectivity involve: (a) testing the existence and significance of the permselectivity barrier on corneal transport of amino acids, and (b) determining the effect of charge type and charge density of amino acids on their absorption. To study the amino acid's charge type and density selectivity, two model amino acids, differing in charge but of similar size, were radioactively labelled and their movements across the cornea were determined with side-by-side diffusion cells. Results from these studies indicate that at physiological pH and pH above the isoelectric point (3.2), the cornea behaves as if it is negatively charged and is thus relatively less permeable to L-glutamic acid (pH 7 and 10) and functions as an ion-exchange membrane for L-lysine (pH 7 and 10). Below the isoelectric point, functional groups become protonated so that the cornea possesses a net positive charge and has the reverse effect on the permeation of L-glutamic acid. However, at low pH, lysine may have a specific effect on the corneal transport mechanism. Utilizing a broad range of hydrophilic polyethylene glycols (PEGs) and electron microscopic studies, the molecular weight dependence of corneal transport and the promoting mechanisms of penetration enhancers, were investigated. Absorption across corneal tissues exhibits a dependence on the molecular weight of PEGs and the molecular weight cutoff is between PEG 400 and PEG 600. Each penetration enhancer was found to affect the cornea and its permeability in a unique manner. Sodium deoxycholate appeared to have little effect on tissue morphology and does not significantly alter the molecular weight permeability profile of the cornea. In contrast, 1 mM digitonin caused severe alteration of the corneal epithelium and also greatly increased the absorption of PEGs. Selective molecular weight effects were seen with 1 mM cytochalasin B and the absorption of the PEG 400 and PEG 600 oligomers increased similar to that of PEG 200. However, the degree of absorption of PEG 1000 did not appear to change over a 4 hour perfusion period. Correlation of mucosal integrity with the effectiveness of cytochalasin B indicates that this agent indeed acts on the tight junction by opening intercellular spaces. The effect of EDTA on the corneal transport of PEG did not significantly affect the molecular weight permeability profile and it may involve some intracellular messengers.
590 $a School code: 0262.
650 4 $a Pharmaceuticals. $3 3562593
690 $a 0572
710 2 $a The University of Wisconsin - Madison. $3 626640
773 0 $t Dissertations Abstracts International $g 54-04B.
790 $a 0262
791 $a Ph.D.
792 $a 1992
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9221491