Saponin Micelles Lead to High Mucosal Permeation and In Vivo Efficacy of Solubilized Budesonide

Autor:	Cornelia Siegl, Sabine Nakowitsch, Nicole Unger-Manhart, Christine Graf, Norman Kirchoff, Jan-Marcus Seifert, Martina Morokutti-Kurz, Marianne Neurath, Christian Knecht, Svenja Sladek, Eva Prieschl-Grassauer, Marielle König-Schuster, Christiane Koller, Andreas Grassauer, Wolfgang Sipos, Elisabeth Foglar
Rok vydání:	2020
Předmět:	Budesonide micelles Mucociliary clearance medicine.medical_treatment drug permeation lcsh:RS1-441 Pharmaceutical Science Mucous membrane of nose 02 engineering and technology Absorption (skin) 030226 pharmacology & pharmacy Article lcsh:Pharmacy and materia medica 03 medical and health sciences 0302 clinical medicine In vivo medicine Chromatography Chemistry technology industry and agriculture local application 021001 nanoscience & nanotechnology Nasal spray tissue availability Nasal administration inflammation mouse model 0210 nano-technology solubilization Ex vivo medicine.drug
Zdroj:	Pharmaceutics, Vol 12, Iss 847, p 847 (2020) Pharmaceutics Volume 12 Issue 9
ISSN:	1999-4923
DOI:	10.3390/pharmaceutics12090847
Popis:	Due to fast nasal mucociliary clearance, only the dissolved drug content can effectively permeate the mucosa and be pharmaceutically active after intranasal application of suspensions. Therefore, the aim of this study was to increase the budesonide concentration in solution of a nasal spray formulation. Budesonide, a highly water-insoluble corticosteroid, was successfully solubilized using a micellar formulation comprising escin, propylene glycol and dexpanthenol in an aqueous buffered environment (&ldquo Budesolv&rdquo ). A formulation based on this micellar system was well-tolerated in the nasal cavity as shown in a good laboratory practice (GLP) local tolerance study in rabbits. Ex vivo permeation studies into porcine nasal mucosa revealed a faster and more efficient absorption. Budesolv with 300 µ g/mL solubilized budesonide resulted in a budesonide concentration of 42 µ g/g tissue after only 15 min incubation. In comparison, incubation with the marketed product Rhinocort® aqua 64 (1.28 mg/mL budesonide as suspension) led to 15 µ g/g tissue. The in vivo tumor-necrosis-factor (TNF)-&alpha secretion in an acute lung inflammation mouse model was significantly reduced (p < 0.001) following a prophylactic treatment with Budesolv compared to Rhinocort® aqua 64. Successful treatment 15 min after the challenge was only possible with Budesolv (40% reduction of TNF-&alpha p = 0.0012) suggesting a faster onset of action. The data reveal that solubilization based on saponin micelles presents an opportunity for the development of products containing hardly soluble substances that result in a faster onset and a better topical treatment effect.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa6cda13ae3b2eb6a4ca31910517c303 https://doi.org/10.3390/pharmaceutics12090847 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.