Thermodynamic and structural aspects of the skin barrier

Bouwstra, Joke A.; Vries, M.A. de; Gooris, Gert S.; Bras, Wim; Brussee, Johannes; Ponec, Maria

doi:10.1016/0168-3659(91)90112-q

Cited by 114 publications

(51 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The stratum corneum is a dead tissue composed of flattened cells filled with crosslinked keratin and an extracellular matrix made up of lipids arranged largely in bilayers (5,6). Unlike the unilamellar phospholipid bilayers of cell membranes, these multilamellar, The publication costs of this article were defrayed in part by page charge payment.…”

mentioning

confidence: 99%

Electroporation of mammalian skin: a mechanism to enhance transdermal drug delivery.

Prausnitz

Bose

Langer

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

576

275

View full text Add to dashboard Cite

Mammalian skin owes its remarkable barrier function to its outermost and dead layer, the stratum corneum. Transdermal transport through this region occurs predominantly through intercellular lipids, organized largely in bilayers. Electroporation is the creation of aqueous pores in lipid bilayers by the application of a short (microseconds to milliseconds) electric pulse. Our measurements suggest that electroporation occurs in the intercellular lipid bilayers of the stratum corneum by a mechanism involving transient structural changes. Flux increases up to 4 orders of magnitude were observed with human skin in vito for three polar molecules having charges between -1 and -4 and molecular weights up to slightly more than 1000. Similar flux increases were observed in vivo with animal skin. These results may have significance for drug delivery and other medical applications.Transdermal drug delivery offers a number of potential advantages over conventional methods, such as pills and injections: (i) no degradation due to stomach, intestine, or first pass of the liver, (ii) probable improved patient compliance because of a user-friendly method, and (iii) potential for steady or time-varying controlled delivery (1-4). Nevertheless, very few drugs can be administered transdermally at therapeutic levels, due to the low permeability and lipophilic nature of human skin. As a result, fewer than 10 drugs are now clinically administered transdermally. However, the market for these drugs exceeds one billion dollars in the United States alone, indicating the importance of this delivery method. Therefore, significant enhancement of transdermal drug delivery has the potential for major impact on medicine.

show abstract

mentioning

confidence: 99%

Electroporation of mammalian skin: a mechanism to enhance transdermal drug delivery.

Prausnitz

Bose

Langer

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

576

275

View full text Add to dashboard Cite

show abstract

“…The presence of fluid domains in the SC matrix is likely also important for other biological functions, for example the enzyme activity in the SC intercellular space (21). There is a rather extensive literature describing how solvents and excipients influence the extracellular solid SC lipids based on studies using scattering, diffraction, and infrared spectroscopy techniques (2,3,5,22,23). Calorimetric studies have further shown that solvents may alter the thermal solid-fluid transitions in SC (2,3,5), which typically occur at nonphysiological elevated temperatures.…”

mentioning

confidence: 99%

Tracking solvents in the skin through atomically resolved measurements of molecular mobility in intact stratum corneum

Pham

Topgaard

Sparr

2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Solvents are commonly used in pharmaceutical and cosmetic formulations and sanitary products and cleansers. The uptake of solvent into the skin may change the molecular organization of skin lipids and proteins, which may in turn alter the protective skin barrier function. We herein examine the molecular effects of 10 different solvents on the outermost layer of skin, the stratum corneum (SC), using polarization transfer solid-state NMR on natural abundance 13C in intact SC. With this approach it is possible to characterize the molecular dynamics of solvent molecules when present inside intact SC and to simultaneously monitor the effects caused by the added solvent on SC lipids and protein components. All solvents investigated cause an increased fluidity of SC lipids, with the most prominent effects shown for the apolar hydrocarbon solvents and 2-propanol. However, no solvent other than water shows the ability to fluidize amino acids in the keratin filaments. The solvent molecules themselves show reduced molecular mobility when incorporated in the SC matrix. Changes in the molecular properties of the SC, and in particular alternation in the balance between solid and fluid SC components, may have significant influences on the macroscopic SC barrier properties as well as mechanical properties of the skin. Deepened understanding of molecular effects of foreign compounds in SC fluidity can therefore have strong impact on the development of skin products in pharmaceutical, cosmetic, and sanitary applications.

show abstract

“…The first lipid-phase transition T 1 at about 408C, which is not easily detectable, could not be found. The a-keratin denaturation peak T 4 , which requires a certain water content of the sample in order to become apparent [14], could not be detected in every thermogram because of the low water content of the samples. Only the second transition T 2 is detectable.…”

Section: Discussionmentioning

confidence: 99%

Laser treatments on skin enhancing and controlling transdermal delivery of 5‐fluorouracil

et al. 2008

View full text Add to dashboard Cite

Background and Objective: Laser ablation of stratum corneum (SC) enhances transdermal delivery of hydrophilic drugs. The influence of the infrared (IR) (l ¼ 1,064 nm), visible (l ¼ 532 nm), and ultraviolet (UV) (l ¼ 355 nm) radiations of a Nd:YAG laser on transdermal delivery of 5-Fluorouracil (5-Fu) across skin was studied in vitro. Materials and Methods: Pinna skin of the inner side of rabbit ear, was used for the skin permeation. The light source for laser treatment was a Q-switched Nd:YAG laser (Lotis TII SL-2132). Ablation thresholds were estimated by using a photoacoustic technique. In addition, permeation study, and morphological and structural skin examination by histology and differential scanning calorimetry (DSC) were carried out. Results: A significant increase in the permeation of 5-Fu across skin pre-treatment with the three different wavelengths studied was obtained. Since irradiation at 1,064 nm allows deep penetration of the radiation, collagen fibers were affected [7.7 J/cm 2 (15 Hz)]. Visible radiation of Nd:YAG laser showed the wider range of fluences (3-8.4 J/cm 2 at 15 Hz) to enhance skin delivery of 5-Fu, without risk of skin lesion. UV radiation required minor energy contribution to produce the same effects within a narrower range of fluences [0.3 J/cm 2 (5 Hz)-1.5 J/cm 2 (15 Hz)] so the process is less controlled and this radiation shows greater impact on the lipidic structure than visible and IR radiations. Conclusions: Use of the visible radiation of a Nd:YAG laser is a good method for improving the efficacy of topical chemotherapy of 5-Fu.

show abstract

Thermodynamic and structural aspects of the skin barrier

Cited by 114 publications

References 16 publications

Electroporation of mammalian skin: a mechanism to enhance transdermal drug delivery.

Electroporation of mammalian skin: a mechanism to enhance transdermal drug delivery.

Tracking solvents in the skin through atomically resolved measurements of molecular mobility in intact stratum corneum

Laser treatments on skin enhancing and controlling transdermal delivery of 5‐fluorouracil

Contact Info

Product

Resources

About