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Electrochemical stability of insulin...

Chen, Yung-Cheng.

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Electrochemical stability of insulin and stabilization for iontophoretic transdermal delivery.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Electrochemical stability of insulin and stabilization for iontophoretic transdermal delivery./
Author:	Chen, Yung-Cheng.
Description:	200 p.
Notes:	Source: Dissertation Abstracts International, Volume: 59-12, Section: B, page: 6279.
Contained By:	Dissertation Abstracts International59-12B.
Subject:	Health Sciences, Pharmacy. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9915424
ISBN:	0599141417

Electrochemical stability of insulin and stabilization for iontophoretic transdermal delivery.
Chen, Yung-Cheng.

Electrochemical stability of insulin and stabilization for iontophoretic transdermal delivery. - 200 p.

Source: Dissertation Abstracts International, Volume: 59-12, Section: B, page: 6279.

Thesis (Ph.D.)--Rutgers The State University of New Jersey - New Brunswick, 1998.

Advancement in biotechnology and understanding of genetics-related diseases have afforded revolution in the development of macromolecular therapeutic agents, namely proteins and polynucleotides. The delivery of such macromolecules is hindered by their physicochemical properties and the barriers resided in the biological systems. Usually these molecules are administered through injection, which is invasive, and having very short biological half-life. Alternative routes and delivery systems have been proposed to achieve a delivery profile that is corresponded to the pharmacodynamical response, such as iontophoretic transdermal delivery system.

ISBN: 0599141417Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Electrochemical stability of insulin and stabilization for iontophoretic transdermal delivery.
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020 $a 0599141417
035 $a (UnM)AAI9915424
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040 $a UnM $c UnM
100 1 $a Chen, Yung-Cheng. $3 1929055
245 1 0 $a Electrochemical stability of insulin and stabilization for iontophoretic transdermal delivery.
300 $a 200 p.
500 $a Source: Dissertation Abstracts International, Volume: 59-12, Section: B, page: 6279.
500 $a Director: Yie W. Chien.
502 $a Thesis (Ph.D.)--Rutgers The State University of New Jersey - New Brunswick, 1998.
520 $a Advancement in biotechnology and understanding of genetics-related diseases have afforded revolution in the development of macromolecular therapeutic agents, namely proteins and polynucleotides. The delivery of such macromolecules is hindered by their physicochemical properties and the barriers resided in the biological systems. Usually these molecules are administered through injection, which is invasive, and having very short biological half-life. Alternative routes and delivery systems have been proposed to achieve a delivery profile that is corresponded to the pharmacodynamical response, such as iontophoretic transdermal delivery system.
520 $a Iontophoresis-facilitated transdermal drug delivery is a technique to increase the transport of charged molecules/ions across the skin, by applying an electric field across the skin to overcome the barrier properties of the stratum corneum, and to modulate the rate of drug permeation. The enhancement of permeation is caused by primarily the electromotive force exerted on the charged molecules under the gradient of electrochemical potential across the skin. There are several aspects of the interactions between protein molecule and the electric field applied, such as the influence of net charges on helical conformation, dipoles of proteins, induction of electroconformational changes and electrochemical coupling, effect on the rate of chemical reactions and energetics of the interaction, and effect of charge accumulation. The structure of protein is known to be intrinsically sensitive to electric fields.
520 $a This dissertation research focuses on the study of effect of electric field on insulin, a therapeutic protein, during iontophoresis, and characterization of the mechanism of electrically-induced insulin degradation to provide means for stabilization of insulin during iontophoresis. The influence of the applied electric field on the physicochemical stability of insulin was demonstrated to be a function of electrical parameters applied and of the solution compositions. The degradation reactions of insulin molecule under an electric potential, as analyzed by UV absorbance-derivative spectrum and HPLC separation, was observed to be greatly facilitated by either a higher electric current/voltage or a longer application period. The observations also indicate that the structure of insulin molecule is undergoing conformational changes resulted from the electrically-induced protein unfolding process. The unfolding/refolding pathways are noted to be related to the reduction of disulfide linkages in insulin structure and are reversible. Incorporation of free sulfhydryl scavenger, such as methionine, along with other stabilizers, such as Pluronic F-127 and glycine, greatly enhance the electrochemical stability of insulin under an electric field.
520 $a It is thus concluded that, under an electrochemical potential, insulin is undergoing reversible disulfide reduction unfolding pathways which process is dependent upon the duration and intensity of electric potential applied. The extent of the electrically-induced insulin degradation can be greatly diminished by incorporation of stabilizers with insulin.
590 $a School code: 0190.
650 4 $a Health Sciences, Pharmacy. $3 1017737
650 4 $a Chemistry, Pharmaceutical. $3 550957
650 4 $a Chemistry, Biochemistry. $3 1017722
690 $a 0572
690 $a 0491
690 $a 0487
710 2 0 $a Rutgers The State University of New Jersey - New Brunswick. $3 1017590
773 0 $t Dissertation Abstracts International $g 59-12B.
790 1 0 $a Chien, Yie W., $e advisor
790 $a 0190
791 $a Ph.D.
792 $a 1998
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9915424