Performance of oral Bosentan-loaded SNEDDS and S-SNEDDS tablets: Biodistribution in mice, echocardiography and histology studies in pulmonary arterial hypertension rat model

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dc.authorid0000-0001-8876-9268
dc.authorid0000-0003-4035-7656
dc.authorid0000-0001-6359-5935
dc.authorid0000-0002-0728-1648
dc.contributor.authorUsta, Duygu Yilmaz
dc.contributor.authorOlgac, Seval
dc.contributor.authorDemirel, Murside Ayse
dc.contributor.authorKula, Serdar
dc.contributor.authorElmas, Cigdem
dc.contributor.authorSezginer, Perihan
dc.contributor.authorKavgaci, Akif
dc.date.accessioned2026-01-24T12:31:08Z
dc.date.available2026-01-24T12:31:08Z
dc.date.issued2025
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractBosentan monohydrate (BOS) is the most preferred molecule for treating the rare pulmonary arterial hypertension (PAH) disease. BOS shows low solubility and high variability when administered orally. This study evaluated the pharmacodynamic biodistribution, echocardiography, and histology results of BOS-loaded SNEDDS and BOS-loaded S-SNEDDS tablets. Pharmacodynamic biodistribution studies were conducted with male Balb/c mice (8 weeks old, 18-20 g) after oral administration. XenoLight (TM) DiR and VivoTag (R) 680XL fluorescent dyes were used to monitor biological distribution and absorption with the In Vivo Imaging System (R) (IVIS (R)). Pharmacodynamic echocardiography and histology studies were carried out with Wistar rats (8-10 weeks old, 250-300 g). The PAH rat model was successfully induced with monocrotaline (MCT), which is one dose (60 mg/kg) was intraperitoneally injected. The reference drug (Tracleer (R) 125 mg tablet) and BOS-loaded SNEDDS and S-SNEDDS tablets were administered as 50 mg/kg; 2 mL per os to the treatment groups. Pharmacodynamic biodistribution studies showed that real-time biodistribution in the body, ex-vivo region of interest (ROI) values of organs, and total fluorescence emission were increased (p < 0.05). It has been confirmed that the formulations enter the systemic circulation via the lymphatic system, do not have a first-pass effect in the liver, and show no emission in the liver. The echocardiographic study was performed for up to 14 days and no difference was found between the treatment groups which are the reference tablet (Tracleer (R)), BOS-loaded SNEDDS, and BOS-loaded S-SNEDDS tablet (p > 0.05). Hematoxylin and Eosin (H&E) and Immunohistochemical (IHC) staining were done for the histology studies. These studies showed that the BOS-loaded formulations have a similar therapeutic effect on histopathological phenomena in lung and liver tissues. As the histological evaluation results, lower-dose formulations were found to be more effective than the same dose reference tablet in terms of improvements in histological parameters (p < 0.05). Comprehensive and comparative in vitro and in vivo studies indicate that BOS-loaded formulations could be an alternative oral drug delivery system for PAH treatment compared to the reference product.
dc.description.sponsorshipScientific and Technological Research Council of Turkiye [217S602]
dc.description.sponsorshipThis study was supported by a grant from The Scientific and Technological Research Council of Turkiye (Project No: 217S602, TUBITAK) . The authors would like to thank Abdi I brahim (Tuerkiye) for providing bosentan monohydrate and Ali Poshtkouh for revising the final draft of this paper.
dc.identifier.doi10.1016/j.ejpb.2025.114725
dc.identifier.issn0939-6411
dc.identifier.issn1873-3441
dc.identifier.pmid40280258
dc.identifier.scopus2-s2.0-105003845053
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.ejpb.2025.114725
dc.identifier.urihttps://hdl.handle.net/20.500.12868/5677
dc.identifier.volume212
dc.identifier.wosWOS:001495127400001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofEuropean Journal of Pharmaceutics and Biopharmaceutics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20260121
dc.subjectBosentan monohydrate
dc.subjectPulmonary arterial hypertension
dc.subjectBiodistribution
dc.subjectEchocardiography
dc.subjectHistology
dc.titlePerformance of oral Bosentan-loaded SNEDDS and S-SNEDDS tablets: Biodistribution in mice, echocardiography and histology studies in pulmonary arterial hypertension rat model
dc.typeArticle

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