Innovative Uses for Zinc in Dermatology

Bae, Yoon Soo; Hill, Nikki D.; Bibi, Yuval; Dreiher, Jacob; Cohen, Arnon D.

doi:10.1016/j.det.2010.03.006

Cited by 34 publications

(43 citation statements)

References 98 publications

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“…Zinc-based compounds designed for topical delivery represent an important class of cutaneous therapeutics designed for photoprotective, antimicrobial, and anti-inflammatory intervention (Guthery et al 2005; Bae et al 2010; Beasley and Meyer 2010). Zinc pyrithione (ZnPT; CAS# 13463-41-7) is a 1:2 complex between a central zinc atom and the membrane permeable ionophore pyrithione (N-hydroxy-2-pyridinethione) (Barnett et al 1977).…”

Section: Introductionmentioning

confidence: 99%

Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis

Lamore

Wondrak

2011

Biometals

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Zinc ion homeostasis plays an important role in human cutaneous biology where it is involved in epidermal differentiation and barrier function, inflammatory and antimicrobial regulation, and wound healing. Zinc-based compounds designed for topical delivery therefore represent an important class of cutaneous therapeutics. Zinc pyrithione (ZnPT) is an FDA-approved microbicidal agent used worldwide in over-the-counter topical antimicrobials, and has also been examined as an investigational therapeutic targeting psoriasis and UVB-induced epidermal hyperplasia. Recently, we have demonstrated that cultured primary human skin keratinocytes display an exquisite sensitivity to nanomolar ZnPT concentrations causing induction of heat shock response gene expression and poly(ADP-ribose) polymerase (PARP)-dependent cell death (Cell Stress Chaperones 15:309–322, 2010). Here we demonstrate that ZnPT causes rapid accumulation of intracellular zinc in primary keratinocytes as observed by quantitative fluorescence microscopy and inductively coupled plasma mass spectrometry (ICP-MS), and that PARP activation, energy crisis, and genomic impairment are all antagonized by zinc chelation. In epidermal reconstructs (EpiDerm™) exposed to topical ZnPT (0.1–2% in Vanicream™), ICP-MS demonstrated rapid zinc accumulation, and expression array analysis demonstrated upregulation of stress response genes encoding metallothionein-2A (MT2A), heat shock proteins (HSPA6, HSPA1A, HSPB5, HSPA1L, DNAJA1, HSPH1, HSPD1, HSPE1), antioxidants (SOD2, GSTM3, HMOX1), and the cell cycle inhibitor p21 (CDKN1A). IHC analysis of ZnPT-treated EpiDerm™ confirmed upregulation of Hsp70 and TUNEL-positivity. Taken together our data demonstrate that ZnPT impairs zinc ion homeostasis and upregulates stress response gene expression in primary keratinocytes and reconstructed human epidermis, activities that may underlie therapeutic and toxicological effects of this topical drug.

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Section: Introductionmentioning

confidence: 99%

Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis

Lamore

Wondrak

2011

Biometals

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“…Every formulation (formulations [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] were prepared mixing evenly 500 mg of albumin (as active ingredient) with 2 or 4 mL of each solvent of table 1 and 2 (as enhancers), to make a lotion, using mechanical overhead mixer (Heidolph, RZR 2020, Germany) at 3000 rpm for 20 minutes.…”

Section: Preparation Of Formulationsmentioning

confidence: 99%

“…Such enhancers include aliphatic acids, fatty acids, esters, alcohols, oils and terpens 1 and also variety of nanoparticle including elemental or polymeric nanoparticles [7][8][9][10][11][12][13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

Untitled

2014

IJPSR

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ABSTRACT:Objectives: Transdermal drug delivery suggests several advantages and has been vastly investigated over last decades. Chemical enhancers improve the quantity of drug penetration through the skin. In this study, hydrophilic solvents have been used as enhancers to promote dermal penetration of albumin. Methods: 20 different formulations containing albumin and hydrophilic solvents were prepared. Transdermal absorption experiments for each formulation were performed using a diffusion cell and a slice of chicken skin as model at 32°C for 3 hours. Samples from the medium were withdrawn and analyzed for albumin concentration. Cumulative amounts of albumin were plotted for each formulation. Results: After 3 hours, 6.8, 5.8, 69.0, 7.9, 11.1, 25.2, 32.0, 98.0, 21.3 and 74.3 mg of albumin were passed through the skin, using formulations containing deionized water (DW), acetic acid, ethyl acetate (EA), methanol, ethanol, 2-propanol, isopropyl alcohol (IPA), glycerol, ethylene glycol (EG) and propylene glycol (PG), respectively. Conclusion: PG, EA and glycerol could act as enhancers for transdermal delivery of albumin. Such delivery was increased using 4 mL of them instead of 2 mL and using exposure time of 3 hours instead of 1.5 hours. The most effective enhancer was found glycerol, showing a maximum albumin permeation of 98.0 mg. Therefore, the study suggested using glycerol as enhancer for transdermal delivery of albumin or other similar proteins in cosmeceutical products.

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“…Parat et al proved that zinc has antioxidant and cytoprotective effects on skin keratinocytes in cell 10 (HaCaT) culture . Zinc Oxide (ZnO) has been applied topically to heal wounds and for treatment of other skin 7,11,12 disorders . The zinc distribution in the skin showed a peak in the epidermal layer decreasing toward the SC, 13 with an exception in the SC which was free of zinc .…”

Section: Introductionmentioning

confidence: 99%

“…It is now believed that formulation components inuence extent and rate of 4 passive transdermal absorption . Permeation of a drug through the skin in the presence of an enhancer is related to chemical structure of enhancer and physicochemical interactions of the enhancer with the drug or [5][6][7] with the skin components . More than 200 chemicals have been shown to enhance skin permeation of drugs.…”

Section: Introductionmentioning

confidence: 99%

Zinc Oxide and Zinc Oxide Nanoparticles as Enhancers in Topical Pharmaceutical and Cosmetic Products

Shokri¹,

Goodarzi²,

Javar³

et al. 2014

Journal of Pharmaceutical Research

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Objectives:Scientists have widely investigated the use of chemical enhancers to improve drug transport through the skin. In this study, ZnO and ZnO nanoparticles (ZnO-NPs) has been used as dermal absorption enhancers for Ibuprofen (IP). Methods:Seven different formulations containing IP, ZnO, or ZnO-NPs were prepared. Dermal absorption experiments were performed at 32°C using a diffusion cell containing phosphate buffer saline (pH 7.4) and a slice of chicken skin. Cumulative amounts of skin permeated IP, ZnO or ZnO-NPs were plotted over time.Results: After 60 minutes, 90, 8 and 81 mg ZnO, ZnO-NPs and IP were passed through the skin, respectively. This amount for IP was 105, 114, 131 and 183 mg in presence of 100 mg ZnO, 100 mg ZnONPs, 200 mg ZnO-NPs, and 500 mg ZnO-NPs, respectively. Maximum amount of not-permeated IP was seen for formulation 1 (IP without enhancer) and minimum notpermeated IP was seen for formulation 5 (IP with 500 mg ZnO-NPs as enhancer). Conclusion:ZnO and more strongly ZnO-NPs could act as enhancers for transdermal delivery of IP. Such effect was improved by increase in concentration of ZnO-NPs. Therefore, ZnO-NPs can be used as enhancer in dermal drug delivery formulations.

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Innovative Uses for Zinc in Dermatology

Cited by 34 publications

References 98 publications

Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis

Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis

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Zinc Oxide and Zinc Oxide Nanoparticles as Enhancers in Topical Pharmaceutical and Cosmetic Products

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