Formulation and Delivery of Topically Applied Drugs for the Treatment of Atopic Eczema and Other Related Diseases

Manda Tsang

Research output: ThesisDoctoral Thesis

Abstract

Atopic eczema is an incurable disorder of the skin. Sufferers are afflicted with hypersensitivity to environmental agents such as soaps (detergents), animal dander, pollen, specific foods and sometimes even water. Genetic mutations in atopic eczema compromise the development of the stratum corneum resulting in xerotic skin that is prone to cracking and increased permeability which leads to irritation due to the influx of exogenous material through the skin. The causes of atopic eczema are due to a combination of genetic and environmental factors and it is, therefore, a difficult disease to manage. Emollients and topical corticosteroids are the mainstay treatments for eczema. However, they do not treat the underlying cause of the flare-ups frequently seen in the condition; the damaged skin barrier. Defects in the skin barrier arise from premature desquamation of the stratum corneum. The main contributors to barrier breakdown are the up-regulation of skin proteases that are located in the skin. Since zinc is a known protease inhibitor, it would thus follow that a topical treatment for skin barrier repair should be developed. Therefore, the main objectives of this thesis are to successfully incorporate zinc into a formulation to develop a novel class of treatment for eczema and to assess the delivery of the element into the skin.

In this thesis, methods to assess and characterise changes to skin barrier function and to extract and quantify zinc in the stratum corneum have been established. The development of two novel topically applied formulations containing zinc lactate as the active ingredient (1% w/w zinc lactate cream and a 2% w/v zinc lactate formulation) has been achieved and the uptake of zinc from the preparations in vitro determined. Further, the in vitro percutaneous penetration of zinc from three commercially available preparations has been investigated and compared to that recovered from the stratum corneum after passive diffusion with the novel zinc formulations. Additionally, in vivo uptake of zinc into human stratum corneum from Sudocremis ® reported. Scanning electron microscopy has revealed the distribution of zinc on the surface of skin treated with various formulations and has also allowed the efficiency of two cleaning procedures to be ascertained.

The delivery of zinc from the novel topical formulation; 1% w/w zinc lactate cream, was more efficient than that the three commercial formulations and shows promise as a new approach to treat atopic eczema.

LanguageEnglish
QualificationPh.D.
Awarding Institution
  • University of Bath
Supervisors/Advisors
  • Guy, Richard, Supervisor
Award date1 Dec 2010
StatusUnpublished - Dec 2010

Fingerprint

Zinc
Skin
Pharmaceutical Preparations
Cornea
Atopic Dermatitis
Lactic Acid
Eczema
Environmental Illness
Dander
Emollients
Soaps
Pollen
Protease Inhibitors
Detergents
Electron Scanning Microscopy
Permeability
Adrenal Cortex Hormones
Peptide Hydrolases
Up-Regulation
Food

Keywords

  • transepidermal water loss
  • zinc lactate
  • zinc
  • Sudocrem
  • stratum lorneum
  • Aqueous Cream BP
  • tape stripping
  • percutaneous penetration
  • SEM
  • atopic eczema
  • ICP-AES

Cite this

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title = "Formulation and Delivery of Topically Applied Drugs for the Treatment of Atopic Eczema and Other Related Diseases",
abstract = "Atopic eczema is an incurable disorder of the skin. Sufferers are afflicted with hypersensitivity to environmental agents such as soaps (detergents), animal dander, pollen, specific foods and sometimes even water. Genetic mutations in atopic eczema compromise the development of the stratum corneum resulting in xerotic skin that is prone to cracking and increased permeability which leads to irritation due to the influx of exogenous material through the skin. The causes of atopic eczema are due to a combination of genetic and environmental factors and it is, therefore, a difficult disease to manage. Emollients and topical corticosteroids are the mainstay treatments for eczema. However, they do not treat the underlying cause of the flare-ups frequently seen in the condition; the damaged skin barrier. Defects in the skin barrier arise from premature desquamation of the stratum corneum. The main contributors to barrier breakdown are the up-regulation of skin proteases that are located in the skin. Since zinc is a known protease inhibitor, it would thus follow that a topical treatment for skin barrier repair should be developed. Therefore, the main objectives of this thesis are to successfully incorporate zinc into a formulation to develop a novel class of treatment for eczema and to assess the delivery of the element into the skin. In this thesis, methods to assess and characterise changes to skin barrier function and to extract and quantify zinc in the stratum corneum have been established. The development of two novel topically applied formulations containing zinc lactate as the active ingredient (1{\%} w/w zinc lactate cream and a 2{\%} w/v zinc lactate formulation) has been achieved and the uptake of zinc from the preparations in vitro determined. Further, the in vitro percutaneous penetration of zinc from three commercially available preparations has been investigated and compared to that recovered from the stratum corneum after passive diffusion with the novel zinc formulations. Additionally, in vivo uptake of zinc into human stratum corneum from Sudocremis {\circledR} reported. Scanning electron microscopy has revealed the distribution of zinc on the surface of skin treated with various formulations and has also allowed the efficiency of two cleaning procedures to be ascertained. The delivery of zinc from the novel topical formulation; 1{\%} w/w zinc lactate cream, was more efficient than that the three commercial formulations and shows promise as a new approach to treat atopic eczema.",
keywords = "transepidermal water loss, zinc lactate, zinc, Sudocrem, stratum lorneum, Aqueous Cream BP, tape stripping, percutaneous penetration, SEM, atopic eczema, ICP-AES",
author = "Manda Tsang",
year = "2010",
month = "12",
language = "English",
school = "University of Bath",

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TY - THES

T1 - Formulation and Delivery of Topically Applied Drugs for the Treatment of Atopic Eczema and Other Related Diseases

AU - Tsang,Manda

PY - 2010/12

Y1 - 2010/12

N2 - Atopic eczema is an incurable disorder of the skin. Sufferers are afflicted with hypersensitivity to environmental agents such as soaps (detergents), animal dander, pollen, specific foods and sometimes even water. Genetic mutations in atopic eczema compromise the development of the stratum corneum resulting in xerotic skin that is prone to cracking and increased permeability which leads to irritation due to the influx of exogenous material through the skin. The causes of atopic eczema are due to a combination of genetic and environmental factors and it is, therefore, a difficult disease to manage. Emollients and topical corticosteroids are the mainstay treatments for eczema. However, they do not treat the underlying cause of the flare-ups frequently seen in the condition; the damaged skin barrier. Defects in the skin barrier arise from premature desquamation of the stratum corneum. The main contributors to barrier breakdown are the up-regulation of skin proteases that are located in the skin. Since zinc is a known protease inhibitor, it would thus follow that a topical treatment for skin barrier repair should be developed. Therefore, the main objectives of this thesis are to successfully incorporate zinc into a formulation to develop a novel class of treatment for eczema and to assess the delivery of the element into the skin. In this thesis, methods to assess and characterise changes to skin barrier function and to extract and quantify zinc in the stratum corneum have been established. The development of two novel topically applied formulations containing zinc lactate as the active ingredient (1% w/w zinc lactate cream and a 2% w/v zinc lactate formulation) has been achieved and the uptake of zinc from the preparations in vitro determined. Further, the in vitro percutaneous penetration of zinc from three commercially available preparations has been investigated and compared to that recovered from the stratum corneum after passive diffusion with the novel zinc formulations. Additionally, in vivo uptake of zinc into human stratum corneum from Sudocremis ® reported. Scanning electron microscopy has revealed the distribution of zinc on the surface of skin treated with various formulations and has also allowed the efficiency of two cleaning procedures to be ascertained. The delivery of zinc from the novel topical formulation; 1% w/w zinc lactate cream, was more efficient than that the three commercial formulations and shows promise as a new approach to treat atopic eczema.

AB - Atopic eczema is an incurable disorder of the skin. Sufferers are afflicted with hypersensitivity to environmental agents such as soaps (detergents), animal dander, pollen, specific foods and sometimes even water. Genetic mutations in atopic eczema compromise the development of the stratum corneum resulting in xerotic skin that is prone to cracking and increased permeability which leads to irritation due to the influx of exogenous material through the skin. The causes of atopic eczema are due to a combination of genetic and environmental factors and it is, therefore, a difficult disease to manage. Emollients and topical corticosteroids are the mainstay treatments for eczema. However, they do not treat the underlying cause of the flare-ups frequently seen in the condition; the damaged skin barrier. Defects in the skin barrier arise from premature desquamation of the stratum corneum. The main contributors to barrier breakdown are the up-regulation of skin proteases that are located in the skin. Since zinc is a known protease inhibitor, it would thus follow that a topical treatment for skin barrier repair should be developed. Therefore, the main objectives of this thesis are to successfully incorporate zinc into a formulation to develop a novel class of treatment for eczema and to assess the delivery of the element into the skin. In this thesis, methods to assess and characterise changes to skin barrier function and to extract and quantify zinc in the stratum corneum have been established. The development of two novel topically applied formulations containing zinc lactate as the active ingredient (1% w/w zinc lactate cream and a 2% w/v zinc lactate formulation) has been achieved and the uptake of zinc from the preparations in vitro determined. Further, the in vitro percutaneous penetration of zinc from three commercially available preparations has been investigated and compared to that recovered from the stratum corneum after passive diffusion with the novel zinc formulations. Additionally, in vivo uptake of zinc into human stratum corneum from Sudocremis ® reported. Scanning electron microscopy has revealed the distribution of zinc on the surface of skin treated with various formulations and has also allowed the efficiency of two cleaning procedures to be ascertained. The delivery of zinc from the novel topical formulation; 1% w/w zinc lactate cream, was more efficient than that the three commercial formulations and shows promise as a new approach to treat atopic eczema.

KW - transepidermal water loss

KW - zinc lactate

KW - zinc

KW - Sudocrem

KW - stratum lorneum

KW - Aqueous Cream BP

KW - tape stripping

KW - percutaneous penetration

KW - SEM

KW - atopic eczema

KW - ICP-AES

M3 - Doctoral Thesis

ER -