Transdermal delivery of antenatal steroids to promote fetal lung maturation: Proof of principle data from sheep and non-human primate models

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dc.coverageDOI: 10.1186/s12916-025-04267-9
dc.creatorCarter, Sean W.D.
dc.creatorBenetti, Ayça Altay
dc.creatorSia, Ryan Tze Liang
dc.creatorPastorin, Giorgia
dc.creatorJohnson, Erin L.
dc.creatorSeah, Kay Yi Michelle
dc.creatorUsuda, Haruo
dc.creatorWatson, Hannah R.S.
dc.creatorKumagai, Yusaku
dc.creatorWei, Qin
dc.creatorLiu, Xiawen
dc.creatorOrefice, Roberto
dc.creatorBon, Marianne
dc.creatorAmin, Zubair
dc.creatorBiswas, Agnihotri
dc.creatorTakahashi, Tsukasa
dc.creatorMochii, Noriyoshi
dc.creatorSaito, Yuya
dc.creatorIkeda, Hideyuki
dc.creatorSaito, Masatoshi
dc.creatorChoolani, Mahesh A.
dc.creatorIllanes, Sebastián E.
dc.creatorKemp, Matthew W.
dc.date2025
dc.date.accessioned2025-11-18T19:56:18Z
dc.date.available2025-11-18T19:56:18Z
dc.description<p>Background: Antenatal steroids (ANS) are routinely administered to women at risk of preterm birth to accelerate fetal lung maturation. Despite extensive clinical use, dosing and route of ANS administration remain unoptimized beyond intramuscular (IM) injection. We aimed to undertake a proof-of-principle assessment of transdermal ANS administration for accelerated fetal lung maturation. Methods: We formulated and tested a transdermal ANS (betamethasone) patch in ex vivo studies. To confirm in vivo transdermal distribution of the ANS patch, we undertook a 24-h pharmacokinetic study in non-pregnant cynomolgus macaques (NHP). To assess the efficacy of transdermal betamethasone on fetal lung maturation, we used a preterm sheep model of pregnancy comparing postnatal ventilation outcomes. Date mated ewes received either of the following: (i) IM normal saline (Saline Control, n = 13); (ii) IM ANS (betamethasone) delivery 2 or 8 days post-treatment (2-Day IM ANS, n = 14; 8-day IM ANS Group, n = 6); (iii) IM saline + 2 × transdermal ANS (Betamethasone) patches delivery 2 days post-treatment (2-Day ANS Patch, n = 10); or (iv) IM saline + 2 × transdermal ANS (betamethasone) patches replaced with 2 × new patches after 48 h, delivery 8 days post-treatment (8-Day ANS Patch, n = 11). Lambs were delivered at 123 ± 1 dGA (term 150 days), then ventilated for 30 min to assess lung maturation status. Arterial blood gas, delivery, and ventilation data were analyzed (p &lt; 0.05 significant). Results: Transdermal administration of ANS in NHPs achieved rapid plasma accumulation, with a plasma half-life of 8.9 h, similar to that achieved with IM dosing in clinical practice. In preterm sheep, all 2- and 8-day IM and transdermal ANS patch groups had clinically important and statistically significant improvements in ventilation parameters (umbilical PaCO<sub>2</sub>, pH, tidal volume) compared to saline control. Conclusions: We demonstrate, for the first time, the potential for using transdermal ANS for preterm fetal lung maturation. Transdermal ANS administration eliminates the need for injections, pain, and infection risk. Moreover, transdermal ANS delivery demonstrates advantages in dose control, continuity of exposure, and potential to remove drug exposure should the risk of preterm birth resolve. Further development of this technology may improve preterm outcomes through delivery of a low dose, constant fetal steroid exposure.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/5c038902-0e49-4312-b1e5-b36663a3ec43
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/59721
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.23 (2025) nr.1 p.452
dc.subjectAntenatal corticosteroids
dc.subjectFetal lung maturation
dc.subjectOptimizing route of administration
dc.subjectPerinatal medicine
dc.subjectPreterm birth
dc.subjectTransdermal patch
dc.titleTransdermal delivery of antenatal steroids to promote fetal lung maturation: Proof of principle data from sheep and non-human primate modelseng
dc.typeArticleeng
dc.typeArtículospa
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