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Topical delivery of a novel antisens...
~
Asbill, Charles Scott.
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Topical delivery of a novel antisense oligonucleotide and validation of a bioengineered skin model.
Record Type:
Language materials, printed : Monograph/item
Title/Author:
Topical delivery of a novel antisense oligonucleotide and validation of a bioengineered skin model./
Author:
Asbill, Charles Scott.
Description:
187 p.
Notes:
Major Professor: Bozena B. Michniak.
Contained By:
Dissertation Abstracts International62-02B.
Subject:
Health Sciences, Pharmacy. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3006004
ISBN:
0493148973
Topical delivery of a novel antisense oligonucleotide and validation of a bioengineered skin model.
Asbill, Charles Scott.
Topical delivery of a novel antisense oligonucleotide and validation of a bioengineered skin model.
- 187 p.
Major Professor: Bozena B. Michniak.
Thesis (Ph.D.)--University of South Carolina, 2000.
During the last decade, research in the area of transdermal and topical drug delivery has expanded greatly. This interest can be attributed to the many advantages offered by this route of administration. Such advantages include but are not limited to: (1) avoidance of the first pass effect; (2) controlled drug release; (3) non-invasive drug delivery and, (4) improved patient compliance.
ISBN: 0493148973Subjects--Topical Terms:
1017737
Health Sciences, Pharmacy.
Topical delivery of a novel antisense oligonucleotide and validation of a bioengineered skin model.
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187 p.
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Major Professor: Bozena B. Michniak.
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Source: Dissertation Abstracts International, Volume: 62-02, Section: B, page: 0802.
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Thesis (Ph.D.)--University of South Carolina, 2000.
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During the last decade, research in the area of transdermal and topical drug delivery has expanded greatly. This interest can be attributed to the many advantages offered by this route of administration. Such advantages include but are not limited to: (1) avoidance of the first pass effect; (2) controlled drug release; (3) non-invasive drug delivery and, (4) improved patient compliance.
520
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Unfortunately, not all drugs can be delivered transdermally due to the complex nature of the skin. It is composed of two primary layers, the epidermis and the underlying dermis. The dermis contains mainly collagen and other matrix proteins, and functions primarily to provide insulation and mechanical support for the overlying epidermal layer. Five primary cell layers make up the epidermis. Its uppermost layer is the stratum corneum. The stratum corneum is the rate limiting step in the diffusion of chemical agents across the skin. The stratum corneum is composed of protein filled cells called corneocytes that are embedded in a lipid matrix. Primary objectives of the research described in this dissertation were to deliver a antisense olignucleotide therapeutic agent across the skin and to examine the ability of a human skin equivalent to serve as an <italic> in vitro</italic> model for transdermal testing.
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The project involving the topical delivery of the antisense oligonucleotide was essentially a drug development project. We evaluated the ability of known permeation enhancers and GRAS (generally regarded as safe) compounds to enhance the delivery of this large molecular weight macromolecule into the skin layers. There was a large initial screeing mode in which the best enhancers were selected for formulation into a cream. Following this there was massive permeability testing, physical stability testing, and biological testing of the products. Currently, the antisense oligonucleotide and cream formulation are being evaluated in clinical trials.
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In order to evaluate the physiology of the skin, skin alternatives have been under development for several years. In this project we set out to develop and screen a skin alternative with properties similar to that of human cadaver skin. In terms of permeability, lipid composition, and histology, human skin has been simulated.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3006004
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