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Verfasst von:Heshmati, Nasim [VerfasserIn]   i
 Wagner, Bjoern [VerfasserIn]   i
 Cheng, Xinlai [VerfasserIn]   i
 Scholz, Therese [VerfasserIn]   i
 Kansy, Manfred [VerfasserIn]   i
 Eisenbrand, Gerhard [VerfasserIn]   i
 Fricker, Gert [VerfasserIn]   i
Titel:Physicochemical characterization and in vitro permeation of an indirubin derivative
Verf.angabe:Nasim Heshmati, Bjoern Wagner, Xinlai Cheng, Therese Scholz, Manfred Kansy, Gerhard Eisenbrand, Gert Fricker
E-Jahr:2013
Jahr:28 August 2013
Umfang:9 S.
Teil:volume:50
 year:2013
 number:3
 pages:467-475
 extent:9
Fussnoten:Gesehen am 29.04.2021
Titel Quelle:Enthalten in: European journal of pharmaceutical sciences
Ort Quelle:New York, NY [u.a.] : Elsevier, 1993
Jahr Quelle:2013
Band/Heft Quelle:50(2013), 3, Seite 467-475
ISSN Quelle:1879-0720
Abstract:The active component of the traditional Chinese medicine, indirubin, exerts anticancer effect on different cancer cell lines. E804, a potent derivative of indirubin inhibits the activation of Stat3 and Stat5 in chronic myelocytic leukaemia (CML) cells. However, physicochemical properties and permeation rate of the compound relevant to the drug formulation have never been reported. Therefore, the ionization constant (pKa), lipophilicity (logD/P), aqueous and organic solubility of E804 and its permeation across Caco-2 cells were investigated. Both high throughput and traditional determinations were used in this study. The Caco-2 cell permeation assay was carried out in Poloxamer 188/HBSS++ solution in order to maintain the solubility of drug. The potential P-gp (P-glycoprotein) interaction for E804 was determined through Calcein-AM uptake assay. The results showed that E804 did not have a detectable pKa in the range of pH 2-11. Log D (distribution coefficient) and Log P (partition coefficient) were determined to be 3.54±0.03. Aqueous solubility test revealed that E804 is practically insoluble in water. Among organic solvents E804 showed the highest solubility in DMSO. The Papp A→B and Papp B→A across Caco-2 cell monolayer were 2.0±0.25×10−6cm/s and 1.14±0.12×10−6cm/s respectively, and the calculated efflux ratio (ER) was 0.57. Calcein-AM uptake assay showed that E804 was not a strong substrate for P-gp. The results indicate that solubility is the major rate limiting step for the drug permeation. The high membrane permeability makes E804 promising for the oral delivery. Therefore, further investigation on solubility of E804 in lipid vehicles is needed to determine an appropriate formulation for the drug.
DOI:doi:10.1016/j.ejps.2013.08.021
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1016/j.ejps.2013.08.021
 Volltext: https://www.sciencedirect.com/science/article/pii/S0928098713003357
 DOI: https://doi.org/10.1016/j.ejps.2013.08.021
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:E804
 Indirubin
 Ionization constant
 Lipophilicity
 logP
 p
K10plus-PPN:1756606293
Verknüpfungen:→ Zeitschrift

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