{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:07:54Z","timestamp":1788858474588,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Turkish Ministry of National Education"},{"id":[{"id":"https:\/\/ror.org\/00jga9g46","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Transdermal delivery of hydrophilic drugs remains limited by poor partitioning into the lipid-rich stratum corneum (SC). This study systematically investigated how ternary nanoemulsion composition and surfactant architecture jointly influence the transdermal delivery of salbutamol and whether the resulting composition\u2013performance relationships are preserved across different skin models. Methods: Salbutamol-loaded nanoemulsions were prepared by the phase inversion temperature (PIT) method across a predefined ternary design space using two non-ionic surfactant systems: polyoxyl castor oil and polyoxyl hydroxystearate. Physicochemical characterization, ternary compositional mapping, in vitro permeation testing, generalized additive modeling (GAM), and attenuated total reflectance\u2013Fourier transform infrared (ATR-FTIR) spectroscopy were combined to evaluate formulation-dependent transport across pig and mouse skin models, complemented by exploratory human-skin experiments. Results: Among the nanoemulsion formulations, pig skin showed the highest salbutamol permeation, with flux values reaching approximately 390 \u00b5g\/cm2\u00b7h. Within the PHS-based system, mouse skin showed lower permeation and a stronger dependence on formulation composition than pig skin, while the simple aqueous vehicle also produced comparatively low permeation in the murine model. The aqueous-vehicle control produced substantially higher permeation than the nanoemulsions in pig skin but lower permeation in mouse skin, while receptor-phase salbutamol concentrations remained below the limit of quantification in human skin. Across both surfactant systems, the most favorable nanoemulsion-mediated permeation was generally associated with water-rich formulations containing comparatively low surfactant levels, whereas highly surfactant-rich regions showed reduced flux despite marked lipid- or protein-associated spectral changes in the descriptive ATR-FTIR analysis. Regression analyses suggested that droplet size and viscosity alone could not consistently explain permeation behavior, whereas compositional modeling revealed pronounced non-linear effects of the water\u2013surfactant\u2013oil balance. Conclusions: Overall, this study demonstrates that nanoemulsion-mediated delivery of hydrophilic drugs is governed primarily by ternary composition, with formulation effects varying across skin models. These findings highlight the importance of composition-based formulation design and appropriate skin-model selection during the development of transdermal systems for hydrophilic drugs.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091127","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:10:22Z","timestamp":1788855022000},"page":"1127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transdermal Delivery of Salbutamol from Nanoemulsions: Influence of Ternary Composition and Surfactant Architecture"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0255-3036","authenticated-orcid":false,"given":"\u00d6zge","family":"Esen Yigit","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, 53121 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"given":"Alf","family":"Lamprecht","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, 53121 Bonn, Germany"},{"name":"EFS, INSERM UMR1098 RIGHT, Universit\u00e9 Marie et Louis Pasteur, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.3109\/10717544.2014.935532","article-title":"Permeation Enhancer Strategies in Transdermal Drug Delivery","volume":"23","author":"Marwah","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40824-021-00226-6","article-title":"Recent Advances in Transdermal Drug Delivery Systems: A Review","volume":"25","author":"Jeong","year":"2021","journal-title":"Biomater. 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