In situ intestinal absorption behaviors of tanshinone IIA from its inclusion complex with hydroxypropyl-beta-cyclodextrin.
In this paper, the intestinal permeability of the inclusion complex of tanshinone IIA (TS IIA) with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated. The corresponding complexation of TS IIA-HP-beta-CD was obtained by coevaporation and characterized by differential scanning calorimetry and X-ray diffraction. The recirculation intestinal perfusion technique in rats was used to study the absorption behavior of free and complexed TS IIA. The change of concentration of TS IIA was separately calculated according to Michaelis-Menten and the Fick's equation to investigate its absorption rate-limiting step. Using the mathematical models above, it was concluded that the limit step to absorption of TS IIA was the dissolution process. Different concentrations of complexed TS IIA were administrated to three intestinal segments, with the intestinal permeability ranging from 3.16x10(-5) cm.s(-1) in the duodenum (50 microg.ml(-1)) to 4.11x10(-5) cm.s(-1) in the jejunum (100 microg.ml(-1)). With the increase of dosage of complex, TS IIA's absorption did not show saturated phenomenon, suggesting its transport mechanism in vivo might primary be passive transport. Besides, the permeability of TS IIA was not apparently influenced by the perfusion section studied, which indicated that there might not exist specific absorption site for TS IIA.
Ling
Wang
W
Institution of Clinical Pharmacological, West China Second University Hospital, Sichuan University, P.R. China.
Rui
Li Chen
LC
Hua
Jiang Xue
JX
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D045784:Abietanes; D000465:Algorithms; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D003627:Data Interpretation, Statistical; D007202:Indicators and Reagents; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D015233:Models, Statistical; D010539:Permeability; D010616:Phenanthrenes / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics*
D045784:Abietanes; D007202:Indicators and Reagents; D010616:Phenanthrenes; D012996:Solutions; D047392:beta-Cyclodextrins; C021751:tanshinone; D000073738:2-Hydroxypropyl-beta-cyclodextrin