Effect of pH on niacinamide skin permeation
(2026) In Scientific Reports 16(1).- Abstract
Niacinamide (NIA) is a widely used skincare ingredient with established benefits for skin barrier support, inflammation reduction, and dermal health. However, the mechanisms governing its transdermal delivery remain insufficiently understood, particularly regarding how formulation pH influences its permeation through the stratum corneum (SC). This study investigates how donor phase pH (5.0 vs. 7.4) modulates NIA skin permeation and how these effects relate to pH induced changes in SC electrical properties. Franz cell diffusion experiments were combined with electrical impedance spectroscopy (EIS) using full‑thickness human skin and 3D reconstructed epidermal tissue models. Permeation was quantified over 24 h and in pH switch... (More)
Niacinamide (NIA) is a widely used skincare ingredient with established benefits for skin barrier support, inflammation reduction, and dermal health. However, the mechanisms governing its transdermal delivery remain insufficiently understood, particularly regarding how formulation pH influences its permeation through the stratum corneum (SC). This study investigates how donor phase pH (5.0 vs. 7.4) modulates NIA skin permeation and how these effects relate to pH induced changes in SC electrical properties. Franz cell diffusion experiments were combined with electrical impedance spectroscopy (EIS) using full‑thickness human skin and 3D reconstructed epidermal tissue models. Permeation was quantified over 24 h and in pH switch experiments, while EIS characterized pH dependent changes in membrane resistance (Rmem) and effective capacitance (Ceff). Additional analyses assessed microbial conversion of NIA to nicotinic acid during prolonged exposure. Neutral donor pH (7.4) increased NIA permeation by roughly twofold compared with acidic pH (5.0) in both membrane types. Correspondingly, pH 7.4 decreased Rmem and increased Ceff, indicating pH driven changes in SC lipid organization and dielectric behavior. These effects were reversible and likely stem from alterations in SC lipid domains, including pH dependent partial deprotonation of free fatty acids that modifies the continuous lipid regions and introduce localized structural microdefects. Such changes enhance NIA and ion permeability and increase SC dielectric properties at neutral pH. Although microbial conversion of NIA to nicotinic acid was negligible within the first 24 h, it became clearly detectable upon prolonged experiments. In conclusion, donor phase pH is a critical determinant of NIA skin permeation, primarily through reversible modulation of SC lipid structure and transport pathways. These findings highlight the importance of pH control in topical formulations and underscore the need to consider microbiota‑mediated transformations when evaluating the efficacy and safety of skin care products containing NIA.
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- author
- Sjöberg, Thomas ; Letasiova, Silvia ; Jankovskaja, Skaidre LU ; Hrapovic, Nina ; Österlund, Christina ; Nilsson, Emelie LU ; Engblom, Johan LU ; Spégel, Peter LU and Björklund, Sebastian LU
- organization
- publishing date
- 2026
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 3D reconstructed epidermis, Electrical impedance spectroscopy, Niacinamide conversion, Nicotinic acid, Skin barrier, Transdermal permeation pathways
- in
- Scientific Reports
- volume
- 16
- issue
- 1
- article number
- 9821
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:105033541993
- pmid:41872243
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-026-41992-4
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The Author(s) 2026.
- id
- 573594df-c0a0-442a-b9c4-f4a6a57b2068
- date added to LUP
- 2026-05-26 13:20:23
- date last changed
- 2026-06-23 14:58:56
@article{573594df-c0a0-442a-b9c4-f4a6a57b2068,
abstract = {{<p>Niacinamide (NIA) is a widely used skincare ingredient with established benefits for skin barrier support, inflammation reduction, and dermal health. However, the mechanisms governing its transdermal delivery remain insufficiently understood, particularly regarding how formulation pH influences its permeation through the stratum corneum (SC). This study investigates how donor phase pH (5.0 vs. 7.4) modulates NIA skin permeation and how these effects relate to pH induced changes in SC electrical properties. Franz cell diffusion experiments were combined with electrical impedance spectroscopy (EIS) using full‑thickness human skin and 3D reconstructed epidermal tissue models. Permeation was quantified over 24 h and in pH switch experiments, while EIS characterized pH dependent changes in membrane resistance (R<sub>mem</sub>) and effective capacitance (C<sub>eff</sub>). Additional analyses assessed microbial conversion of NIA to nicotinic acid during prolonged exposure. Neutral donor pH (7.4) increased NIA permeation by roughly twofold compared with acidic pH (5.0) in both membrane types. Correspondingly, pH 7.4 decreased R<sub>mem</sub> and increased C<sub>eff</sub>, indicating pH driven changes in SC lipid organization and dielectric behavior. These effects were reversible and likely stem from alterations in SC lipid domains, including pH dependent partial deprotonation of free fatty acids that modifies the continuous lipid regions and introduce localized structural microdefects. Such changes enhance NIA and ion permeability and increase SC dielectric properties at neutral pH. Although microbial conversion of NIA to nicotinic acid was negligible within the first 24 h, it became clearly detectable upon prolonged experiments. In conclusion, donor phase pH is a critical determinant of NIA skin permeation, primarily through reversible modulation of SC lipid structure and transport pathways. These findings highlight the importance of pH control in topical formulations and underscore the need to consider microbiota‑mediated transformations when evaluating the efficacy and safety of skin care products containing NIA.</p>}},
author = {{Sjöberg, Thomas and Letasiova, Silvia and Jankovskaja, Skaidre and Hrapovic, Nina and Österlund, Christina and Nilsson, Emelie and Engblom, Johan and Spégel, Peter and Björklund, Sebastian}},
issn = {{2045-2322}},
keywords = {{3D reconstructed epidermis; Electrical impedance spectroscopy; Niacinamide conversion; Nicotinic acid; Skin barrier; Transdermal permeation pathways}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Effect of pH on niacinamide skin permeation}},
url = {{http://dx.doi.org/10.1038/s41598-026-41992-4}},
doi = {{10.1038/s41598-026-41992-4}},
volume = {{16}},
year = {{2026}},
}