Microvesicle Formulations and Contact Allergy - Experimental Studies in In-Vitro, Mice and Man

Jakob Torp Madsen

Publikation: Bog/antologi/afhandling/rapportPh.d.-afhandlingForskning

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Resumé

Attempts to improve formulation of topical products are a continuing process i.e. to increase cosmetic
performance, enhance effects and protect ingredients from degradation. The development of micro and
nano-vesicular systems has lead to marketing of topical drugs and cosmetics using these technologies.
Several papers have reported improved clinical efficacy by encapsulating pharmaceuticals in vesicular
systems. Some vesicular systems may improve transdermal delivery of compounds compared to
conventional vehicles. Few case reports have suggested that microvesicle formulations may affect
allergenicity of topical products.
The aim of this thesis is to investigate the effect on the sensitizing and elicitation capacity of chemical
allergens encapsulated in vesicular systems.
The first part examined how the encapsulation of isoeugenol, dinitro-chloro-benzene, and potassium
dichromate in liposomes, ethosomes and polycaprolactone affects the sensitizing properties using the
OECD and FDA approved skin sensitisation test method in mice: the Local Lymph Node Assay.
Ethanolic liposome (Ethosome) formulation of lipophilic allergens increased the sensitising capacity
and polycaprolactone protected against sensitisation compared to conventional vehicles. The
formulation of the hydrophilic allergen, potassium dichromate, in all three drug delivery systems did
not affect the sensitisation capacity. Further, the effect of vesicle size was studied and conflicting
results were found.
The second part examined whether encapsulation of allergens in ethosomes affects the patch test
reactivity and outcome of the Repeated Open Application Test (ROAT) compared to test with
ethanol:water formulations. Pre-sensitized volunteer individuals were patch tested with a dilution
series of isoeugenol and methyldibromoglutaronitrile formulated in ethosomes and ethanol:water. Both
contact allergens encapsulated in ethosomes showed significantly enhanced patch test reactions
compared to the allergen preparation in ethanol:water without ethosomes. No significant difference in
the median lag time was recorded between preparations in the repeated open application test.
The third part examined the percutaneous absorption in vitro of dinitro-chloro-benzene and
isoeugenol formulated in ethosomes and ethanol:water using Franz cells and human cadaver skin. We
found no significant relationship between percutaneous skin absorption /penetration of the allergens
and the sensitising properties of the test formulations.

Conclusion
Encapsulation of lipophilic contact allergens in lipid vesicles and nanospheres may affect the
sensitising and elicitation capacity of the encapsulated allergen. Encapsulation of the hydrophilic
allergen potassium dichromate did not alter the sensitizing capacity in the Local Lymph Node Assay.
We did not find a correlation between the percutaneous skin absorption/penetration pattern and the
sensitising capacity. The clinical implications of these results are so far uncertain. However, the
cosmetic industry should consider the effect of encapsulation on a case by case basis because certain
ingredients may become more allergenic when encapsulated. Dermatologists investigating patients
with allergic reactions to consumer products using encapsulation technology should consider the risk
of false negative results, if testing with ingredients in conventional patch test vehicles. Testing with
encapsulated ingredients should be performed when possible.
OriginalsprogEngelsk
ForlagSyddansk Universitet. Det Sundhedsvidenskabelige Fakultet
Antal sider99
StatusUdgivet - 2011

Fingeraftryk

Skin Absorption
Allergens
Hypersensitivity
Potassium Dichromate
Patch Tests
Ethanol
In Vitro Techniques
Marketing
Pharmaceutical Preparations
Volunteers
Lipids
Skin

Citer dette

Madsen, J. T. (2011). Microvesicle Formulations and Contact Allergy - Experimental Studies in In-Vitro, Mice and Man. Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet.
Madsen, Jakob Torp. / Microvesicle Formulations and Contact Allergy - Experimental Studies in In-Vitro, Mice and Man. Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet, 2011. 99 s.
@phdthesis{a7ed34b9576144118a79d1f2c856b62f,
title = "Microvesicle Formulations and Contact Allergy - Experimental Studies in In-Vitro, Mice and Man",
abstract = "Attempts to improve formulation of topical products are a continuing process i.e. to increase cosmeticperformance, enhance effects and protect ingredients from degradation. The development of micro andnano-vesicular systems has lead to marketing of topical drugs and cosmetics using these technologies.Several papers have reported improved clinical efficacy by encapsulating pharmaceuticals in vesicularsystems. Some vesicular systems may improve transdermal delivery of compounds compared toconventional vehicles. Few case reports have suggested that microvesicle formulations may affectallergenicity of topical products.The aim of this thesis is to investigate the effect on the sensitizing and elicitation capacity of chemicalallergens encapsulated in vesicular systems.The first part examined how the encapsulation of isoeugenol, dinitro-chloro-benzene, and potassiumdichromate in liposomes, ethosomes and polycaprolactone affects the sensitizing properties using theOECD and FDA approved skin sensitisation test method in mice: the Local Lymph Node Assay.Ethanolic liposome (Ethosome) formulation of lipophilic allergens increased the sensitising capacityand polycaprolactone protected against sensitisation compared to conventional vehicles. Theformulation of the hydrophilic allergen, potassium dichromate, in all three drug delivery systems didnot affect the sensitisation capacity. Further, the effect of vesicle size was studied and conflictingresults were found.The second part examined whether encapsulation of allergens in ethosomes affects the patch testreactivity and outcome of the Repeated Open Application Test (ROAT) compared to test withethanol:water formulations. Pre-sensitized volunteer individuals were patch tested with a dilutionseries of isoeugenol and methyldibromoglutaronitrile formulated in ethosomes and ethanol:water. Bothcontact allergens encapsulated in ethosomes showed significantly enhanced patch test reactionscompared to the allergen preparation in ethanol:water without ethosomes. No significant difference inthe median lag time was recorded between preparations in the repeated open application test.The third part examined the percutaneous absorption in vitro of dinitro-chloro-benzene andisoeugenol formulated in ethosomes and ethanol:water using Franz cells and human cadaver skin. Wefound no significant relationship between percutaneous skin absorption /penetration of the allergensand the sensitising properties of the test formulations.ConclusionEncapsulation of lipophilic contact allergens in lipid vesicles and nanospheres may affect thesensitising and elicitation capacity of the encapsulated allergen. Encapsulation of the hydrophilicallergen potassium dichromate did not alter the sensitizing capacity in the Local Lymph Node Assay.We did not find a correlation between the percutaneous skin absorption/penetration pattern and thesensitising capacity. The clinical implications of these results are so far uncertain. However, thecosmetic industry should consider the effect of encapsulation on a case by case basis because certainingredients may become more allergenic when encapsulated. Dermatologists investigating patientswith allergic reactions to consumer products using encapsulation technology should consider the riskof false negative results, if testing with ingredients in conventional patch test vehicles. Testing withencapsulated ingredients should be performed when possible.",
author = "Madsen, {Jakob Torp}",
year = "2011",
language = "English",
publisher = "Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet",

}

Madsen, JT 2011, Microvesicle Formulations and Contact Allergy - Experimental Studies in In-Vitro, Mice and Man. Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet.

Microvesicle Formulations and Contact Allergy - Experimental Studies in In-Vitro, Mice and Man. / Madsen, Jakob Torp.

Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet, 2011. 99 s.

Publikation: Bog/antologi/afhandling/rapportPh.d.-afhandlingForskning

TY - BOOK

T1 - Microvesicle Formulations and Contact Allergy - Experimental Studies in In-Vitro, Mice and Man

AU - Madsen, Jakob Torp

PY - 2011

Y1 - 2011

N2 - Attempts to improve formulation of topical products are a continuing process i.e. to increase cosmeticperformance, enhance effects and protect ingredients from degradation. The development of micro andnano-vesicular systems has lead to marketing of topical drugs and cosmetics using these technologies.Several papers have reported improved clinical efficacy by encapsulating pharmaceuticals in vesicularsystems. Some vesicular systems may improve transdermal delivery of compounds compared toconventional vehicles. Few case reports have suggested that microvesicle formulations may affectallergenicity of topical products.The aim of this thesis is to investigate the effect on the sensitizing and elicitation capacity of chemicalallergens encapsulated in vesicular systems.The first part examined how the encapsulation of isoeugenol, dinitro-chloro-benzene, and potassiumdichromate in liposomes, ethosomes and polycaprolactone affects the sensitizing properties using theOECD and FDA approved skin sensitisation test method in mice: the Local Lymph Node Assay.Ethanolic liposome (Ethosome) formulation of lipophilic allergens increased the sensitising capacityand polycaprolactone protected against sensitisation compared to conventional vehicles. Theformulation of the hydrophilic allergen, potassium dichromate, in all three drug delivery systems didnot affect the sensitisation capacity. Further, the effect of vesicle size was studied and conflictingresults were found.The second part examined whether encapsulation of allergens in ethosomes affects the patch testreactivity and outcome of the Repeated Open Application Test (ROAT) compared to test withethanol:water formulations. Pre-sensitized volunteer individuals were patch tested with a dilutionseries of isoeugenol and methyldibromoglutaronitrile formulated in ethosomes and ethanol:water. Bothcontact allergens encapsulated in ethosomes showed significantly enhanced patch test reactionscompared to the allergen preparation in ethanol:water without ethosomes. No significant difference inthe median lag time was recorded between preparations in the repeated open application test.The third part examined the percutaneous absorption in vitro of dinitro-chloro-benzene andisoeugenol formulated in ethosomes and ethanol:water using Franz cells and human cadaver skin. Wefound no significant relationship between percutaneous skin absorption /penetration of the allergensand the sensitising properties of the test formulations.ConclusionEncapsulation of lipophilic contact allergens in lipid vesicles and nanospheres may affect thesensitising and elicitation capacity of the encapsulated allergen. Encapsulation of the hydrophilicallergen potassium dichromate did not alter the sensitizing capacity in the Local Lymph Node Assay.We did not find a correlation between the percutaneous skin absorption/penetration pattern and thesensitising capacity. The clinical implications of these results are so far uncertain. However, thecosmetic industry should consider the effect of encapsulation on a case by case basis because certainingredients may become more allergenic when encapsulated. Dermatologists investigating patientswith allergic reactions to consumer products using encapsulation technology should consider the riskof false negative results, if testing with ingredients in conventional patch test vehicles. Testing withencapsulated ingredients should be performed when possible.

AB - Attempts to improve formulation of topical products are a continuing process i.e. to increase cosmeticperformance, enhance effects and protect ingredients from degradation. The development of micro andnano-vesicular systems has lead to marketing of topical drugs and cosmetics using these technologies.Several papers have reported improved clinical efficacy by encapsulating pharmaceuticals in vesicularsystems. Some vesicular systems may improve transdermal delivery of compounds compared toconventional vehicles. Few case reports have suggested that microvesicle formulations may affectallergenicity of topical products.The aim of this thesis is to investigate the effect on the sensitizing and elicitation capacity of chemicalallergens encapsulated in vesicular systems.The first part examined how the encapsulation of isoeugenol, dinitro-chloro-benzene, and potassiumdichromate in liposomes, ethosomes and polycaprolactone affects the sensitizing properties using theOECD and FDA approved skin sensitisation test method in mice: the Local Lymph Node Assay.Ethanolic liposome (Ethosome) formulation of lipophilic allergens increased the sensitising capacityand polycaprolactone protected against sensitisation compared to conventional vehicles. Theformulation of the hydrophilic allergen, potassium dichromate, in all three drug delivery systems didnot affect the sensitisation capacity. Further, the effect of vesicle size was studied and conflictingresults were found.The second part examined whether encapsulation of allergens in ethosomes affects the patch testreactivity and outcome of the Repeated Open Application Test (ROAT) compared to test withethanol:water formulations. Pre-sensitized volunteer individuals were patch tested with a dilutionseries of isoeugenol and methyldibromoglutaronitrile formulated in ethosomes and ethanol:water. Bothcontact allergens encapsulated in ethosomes showed significantly enhanced patch test reactionscompared to the allergen preparation in ethanol:water without ethosomes. No significant difference inthe median lag time was recorded between preparations in the repeated open application test.The third part examined the percutaneous absorption in vitro of dinitro-chloro-benzene andisoeugenol formulated in ethosomes and ethanol:water using Franz cells and human cadaver skin. Wefound no significant relationship between percutaneous skin absorption /penetration of the allergensand the sensitising properties of the test formulations.ConclusionEncapsulation of lipophilic contact allergens in lipid vesicles and nanospheres may affect thesensitising and elicitation capacity of the encapsulated allergen. Encapsulation of the hydrophilicallergen potassium dichromate did not alter the sensitizing capacity in the Local Lymph Node Assay.We did not find a correlation between the percutaneous skin absorption/penetration pattern and thesensitising capacity. The clinical implications of these results are so far uncertain. However, thecosmetic industry should consider the effect of encapsulation on a case by case basis because certainingredients may become more allergenic when encapsulated. Dermatologists investigating patientswith allergic reactions to consumer products using encapsulation technology should consider the riskof false negative results, if testing with ingredients in conventional patch test vehicles. Testing withencapsulated ingredients should be performed when possible.

M3 - Ph.D. thesis

BT - Microvesicle Formulations and Contact Allergy - Experimental Studies in In-Vitro, Mice and Man

PB - Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet

ER -

Madsen JT. Microvesicle Formulations and Contact Allergy - Experimental Studies in In-Vitro, Mice and Man. Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet, 2011. 99 s.