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Novel Strategy for the Systemic Delivery of Furosemide Based on a New Drug Transport Mechanism.
- Source :
-
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2018; Vol. 41 (12), pp. 1769-1777. - Publication Year :
- 2018
-
Abstract
- We reported a novel transport mechanism of curcumin, independent of improved solubility, which involved direct contact of amorphous solid particles with the cell membrane. This mechanism has potential as a novel systemic delivery system of poorly water-soluble drugs. In this study, the transport mechanism of furosemide (FUR), which is transported by the same novel mechanism, was examined. In vitro cell permeation studies under air-interface conditions (AICs) revealed that the permeation from powders sprayed on cell monolayers was significantly higher than that under liquid-covered conditions (LCCs) from their solutions. The permeation from amorphous solid particles was faster than that from crystals. Similar results were derived from in vitro studies using an artificial membrane, with which the permeation of FUR could be examined without water. These findings clearly indicated that the transport mechanism of FUR is the same as that of curcumin. For the application of this new transport mechanism, the in vivo absorption of FUR was examined after pulmonary insufflation, which allows the solid particles to make direct contact with the epithelial cells. Pulmonary absorption of FUR from the amorphous powder was almost complete and was faster than that after intragastric administration of the solution, suggesting that FUR was absorbed from the lung by the same mechanism as the in vitro study. This new transport mechanism, which is independent of water dissolution, could be exploited to develop a novel delivery system for poorly water-soluble drugs, using pulmonary powder inhalation.
- Subjects :
- Administration, Oral
Animals
Cell Membrane metabolism
Chromatography, High Pressure Liquid
Dogs
Epithelial Cells metabolism
Furosemide administration & dosage
Furosemide blood
Furosemide chemistry
Infusions, Intravenous
Madin Darby Canine Kidney Cells
Male
Powders
Rats, Wistar
Solubility
Surface Properties
Cell Membrane drug effects
Cell Membrane Permeability drug effects
Epithelial Cells drug effects
Furosemide pharmacokinetics
Membranes, Artificial
Subjects
Details
- Language :
- English
- ISSN :
- 1347-5215
- Volume :
- 41
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Biological & pharmaceutical bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 30504679
- Full Text :
- https://doi.org/10.1248/bpb.b18-00315