Sugar-branched-cyclodextrins as injectable drug carriers in mice

Citation
T. Shinoda et al., Sugar-branched-cyclodextrins as injectable drug carriers in mice, DRUG DEV IN, 25(11), 1999, pp. 1185-1192
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
ISSN journal
0363-9045 → ACNP
Volume
25
Issue
11
Year of publication
1999
Pages
1185 - 1192
Database
ISI
SICI code
0363-9045(1999)25:11<1185:SAIDCI>2.0.ZU;2-Z
Abstract
The purpose of this study was to investigate stable complexation of drug in blood by sugar-branched-beta-cyclodextrins (beta-CDs) such as glucose (glu )-or galactose (gal)-branched-beta-CDs and the pharmacokinetic disposition of drug in sugar-branched-beta-CD complex. Complexation of steroidal drugs in sugar-branched-beta-CDs and their replacement by cholesterol were measur ed. The complexes of dexamethasone/glucosyl-beta-CDs (dexamethasone/glu-bet a-CD or dexamethasone/glu-glu-beta-CD) were not replaced by cholesterol, wh ich is a representative endogenous compound, whereas the complex of dexamet hasone/beta-CD was replaced by cholesterol. The same results were obtained in steroidal drugs such as hydrocortisone, triamcinolone, and prednisolone. Thus, the use of glu-beta-CD and glu-glu-beta-CD permitted the stable comp lexation of the drug in water. Stability constants of dexamethasone/glu-glu -beta-CD and dexamethasone/gal-glu-beta-CD complexes are the same, which me ans that the sugar moiety of the side chain in beta-CD has little effect on stability constants. After the dexamethasone/gal-glu-beta-CD complex or th e dexamethasone/glu-glu-beta-CD complex (dexamethasone: 1 mg/body) was admi nistered intravenously to mice, dexamethasone concentrations in liver tissu e and blood were measured. The dexamethasone/gal-glu-beta-CD complex (66.1 +/- 1.7 mu g as dexamethasone/gram of liver tissue) was distributed to live r tissue significantly more than the dexamethasone/glu-glu-beta-CD (beta-CD ) complex (59.9 +/- 1.0 mu g as dexamethasone/gram of liver) at 30 min afte r administration (p < .05). Sugar-branched-beta-CD gave a water-soluble and stable complex for dexamethasone and changed the disposition of dexamethas one. Sugar-branched-beta-CDs are potentially excellent carriers for a stero idal injectable formulation.