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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 724001.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Characterization of lung-delivered in-situ forming controlled release formulations
Authors:Dalla-Bona, A. C.; Stoisiek, K.; Oesterheld, N.; Schmehl, T.; Gessler, T.; Seeger, W.; Beck-Broichsitter, M.
Date of Publication (YYYY-MM-DD):2015-10
Title of Journal:J Pharm Pharmacol
Volume:67
Issue / Number:10
Start Page:1349
End Page:1354
Audience:Not Specified
Abstract / Description:OBJECTIVES: This study investigated the controlled drug release potential of formulations revealing temperature-induced sol-gel transition following administration to the respiratory tract. METHODS: Diverse sildenafil-containing aqueous poloxamer 407 preparations were evaluated for critical gelation temperature and rheological properties. The in-vitro drug release profiles of the in-situ forming formulations were studied in a Franz type cell, while the drug absorption characteristics were determined in an isolated lung model. Furthermore, the weight gain of isolated lungs was monitored and the bronchoalveolar lavage fluid was analysed for the total protein content. KEY FINDINGS: Poloxamer 407 solutions with concentrations of >12 wt.% revealed gelation upon temperature increase (>20 degrees C). Compared with free sildenafil solution, sildenafil-containing polymer formulations showed a prolonged in-vitro drug release profile. Likewise, 17 and 21 wt.% of poloxamer 407 were characterized by a sustained sildenafil transfer from the lung into the perfusate. However, a 10 wt.% polymer solution displayed an immediate sildenafil absorption. Interestingly, increasing the poloxamer 407 concentration (21 and 17 vs. 10 wt.%) led to decreased organ weight gain kinetics and a lower total protein content found in the bronchoalveolar lavage fluid. CONCLUSIONS: In-situ forming controlled release hydrogels represent a viable approach for inhalative therapy.
Free Keywords:controlled drug delivery; isolated rabbit lung; poloxamer 407; sildenafil; sol-gel transition
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:2042-7158 (Electronic) 0022-3573 (Linking) %R 10.1111/jphp.12434
URL:http://www.ncbi.nlm.nih.gov/pubmed/25920623
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