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Topically applied lipid-containing emulsions based on PEGylated emulsifiers: Formulation, characterization, and evaluation of their impact on skin properties ex vivo and in vivo

Authorized Users Only
2022
Authors
Liu, Yali
Ilić, Tanja
Pantelić, Ivana
Savić, Snežana
Lunter, Dominique Jasmin
Article (Published version)
Metadata
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Abstract
PEGylated emulsifiers have been largely used in topical formulations for skin research. They have been a continuous study focus in our group as well. According to our previous studies, severe interruptions of the skin barrier were observed with certain types of emulsifiers. To restore the skin barrier function and counteract the effects of emulsifiers, we considered topically delivering lipids into the lipid matrix of the SC. Herein, PEG-20 cetyl ether (C20) -based oil-in-water (O/W) emulsions were developed owing to the stronger interactions of C20 with skin. The lipids containing ceramides (Cers), palmitic acids (PA), and cholesterol with different ratios and combinations were merged into the base emulsion. PEG-40 stearyl ether (S40)-based emulsion was used as a reference as S40 showed negligible impact on SC lipids. The evaluations were conducted ex vivo with confocal Raman spectroscopy (CRS) regarding the SC lipid, SC thickness, and skin penetration properties. In parallel, the in ...vivo irritation studies were also implemented including the transepidermal-water-loss (TEWL), skin hydration, and erythema index. The results indicated less SC lipid extraction of topically delivered lipids on ex vivo porcine skin with the addition and ratio of incorporated Cers influencing the extent of formulations counteracting the skin interruption by C20. The ex vivo penetration study showed a similar trend in drug penetration depths. In regards to the in vivo studies, TEWL was demonstrated to be suitable for differentiating the impact on skin barrier properties. The in vivo observations were generally correlated with the ex vivo results. The exact findings in this research can lead us to a better selection of applied lipid components and compositions. Future research will elucidate which type of Cer was predominantly extracted by C20, advancing future formulation development.

Keywords:
Ceramides / Confocal Raman spectroscopy / Oil-in-water emulsion / PEG-20 cetyl ether / Skin penetration / Stratum corneum
Source:
International Journal of Pharmaceutics, 2022, 626
Publisher:
  • Elsevier B.V.
Funding / projects:
  • The in-vivo study was part of a bilateral project supported by the German Academic Exchange Service (DAAD, project number: 57514345)
  • Ministry of Education, Science, and Technological Development of the Republic of Serbia through bilateral project between Serbia and Ger- many (grant number: 451-03-01855/2019-09/12)

DOI: 10.1016/j.ijpharm.2022.122202

ISSN: 0378-5173

Scopus: 2-s2.0-85138151026
[ Google Scholar ]
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/4278
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Liu, Yali
AU  - Ilić, Tanja
AU  - Pantelić, Ivana
AU  - Savić, Snežana
AU  - Lunter, Dominique Jasmin
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4278
AB  - PEGylated emulsifiers have been largely used in topical formulations for skin research. They have been a continuous study focus in our group as well. According to our previous studies, severe interruptions of the skin barrier were observed with certain types of emulsifiers. To restore the skin barrier function and counteract the effects of emulsifiers, we considered topically delivering lipids into the lipid matrix of the SC. Herein, PEG-20 cetyl ether (C20) -based oil-in-water (O/W) emulsions were developed owing to the stronger interactions of C20 with skin. The lipids containing ceramides (Cers), palmitic acids (PA), and cholesterol with different ratios and combinations were merged into the base emulsion. PEG-40 stearyl ether (S40)-based emulsion was used as a reference as S40 showed negligible impact on SC lipids. The evaluations were conducted ex vivo with confocal Raman spectroscopy (CRS) regarding the SC lipid, SC thickness, and skin penetration properties. In parallel, the in vivo irritation studies were also implemented including the transepidermal-water-loss (TEWL), skin hydration, and erythema index. The results indicated less SC lipid extraction of topically delivered lipids on ex vivo porcine skin with the addition and ratio of incorporated Cers influencing the extent of formulations counteracting the skin interruption by C20. The ex vivo penetration study showed a similar trend in drug penetration depths. In regards to the in vivo studies, TEWL was demonstrated to be suitable for differentiating the impact on skin barrier properties. The in vivo observations were generally correlated with the ex vivo results. The exact findings in this research can lead us to a better selection of applied lipid components and compositions. Future research will elucidate which type of Cer was predominantly extracted by C20, advancing future formulation development.
PB  - Elsevier B.V.
T2  - International Journal of Pharmaceutics
T1  - Topically applied lipid-containing emulsions based on PEGylated emulsifiers: Formulation, characterization, and evaluation of their impact on skin properties ex vivo and in vivo
VL  - 626
DO  - 10.1016/j.ijpharm.2022.122202
ER  - 
@article{
author = "Liu, Yali and Ilić, Tanja and Pantelić, Ivana and Savić, Snežana and Lunter, Dominique Jasmin",
year = "2022",
abstract = "PEGylated emulsifiers have been largely used in topical formulations for skin research. They have been a continuous study focus in our group as well. According to our previous studies, severe interruptions of the skin barrier were observed with certain types of emulsifiers. To restore the skin barrier function and counteract the effects of emulsifiers, we considered topically delivering lipids into the lipid matrix of the SC. Herein, PEG-20 cetyl ether (C20) -based oil-in-water (O/W) emulsions were developed owing to the stronger interactions of C20 with skin. The lipids containing ceramides (Cers), palmitic acids (PA), and cholesterol with different ratios and combinations were merged into the base emulsion. PEG-40 stearyl ether (S40)-based emulsion was used as a reference as S40 showed negligible impact on SC lipids. The evaluations were conducted ex vivo with confocal Raman spectroscopy (CRS) regarding the SC lipid, SC thickness, and skin penetration properties. In parallel, the in vivo irritation studies were also implemented including the transepidermal-water-loss (TEWL), skin hydration, and erythema index. The results indicated less SC lipid extraction of topically delivered lipids on ex vivo porcine skin with the addition and ratio of incorporated Cers influencing the extent of formulations counteracting the skin interruption by C20. The ex vivo penetration study showed a similar trend in drug penetration depths. In regards to the in vivo studies, TEWL was demonstrated to be suitable for differentiating the impact on skin barrier properties. The in vivo observations were generally correlated with the ex vivo results. The exact findings in this research can lead us to a better selection of applied lipid components and compositions. Future research will elucidate which type of Cer was predominantly extracted by C20, advancing future formulation development.",
publisher = "Elsevier B.V.",
journal = "International Journal of Pharmaceutics",
title = "Topically applied lipid-containing emulsions based on PEGylated emulsifiers: Formulation, characterization, and evaluation of their impact on skin properties ex vivo and in vivo",
volume = "626",
doi = "10.1016/j.ijpharm.2022.122202"
}
Liu, Y., Ilić, T., Pantelić, I., Savić, S.,& Lunter, D. J.. (2022). Topically applied lipid-containing emulsions based on PEGylated emulsifiers: Formulation, characterization, and evaluation of their impact on skin properties ex vivo and in vivo. in International Journal of Pharmaceutics
Elsevier B.V.., 626.
https://doi.org/10.1016/j.ijpharm.2022.122202
Liu Y, Ilić T, Pantelić I, Savić S, Lunter DJ. Topically applied lipid-containing emulsions based on PEGylated emulsifiers: Formulation, characterization, and evaluation of their impact on skin properties ex vivo and in vivo. in International Journal of Pharmaceutics. 2022;626.
doi:10.1016/j.ijpharm.2022.122202 .
Liu, Yali, Ilić, Tanja, Pantelić, Ivana, Savić, Snežana, Lunter, Dominique Jasmin, "Topically applied lipid-containing emulsions based on PEGylated emulsifiers: Formulation, characterization, and evaluation of their impact on skin properties ex vivo and in vivo" in International Journal of Pharmaceutics, 626 (2022),
https://doi.org/10.1016/j.ijpharm.2022.122202 . .

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