Study on the intestinal absorption profiles of tanshinone IIA and its inclusion complex with cyclodextrin in rats.
In this paper, the effect of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the intestinal permeability of the tanshinone IIA (TS) was investigated. The inclusion complex was obtained at the molar ratio of 1:1 by lyophilization and characterized by differential scanning calorimetry and phase solubility studies. Using the in situ intestinal perfusion technique, the absorption behaviors of TS and its inclusion complex were investigated at a series of concentration levels in three separate segments of the small intestine. Using the perfusion model, it was demonstrated that the absorption of TS, whether it was free or complexed, was independent of both the concentration and the intestinal site. The permeability rates of TS across the intestinal epithelial membrane were enhanced about 7 times and the fraction absorbed was increased approximately 9-fold by the formation of the inclusion complex with HP-beta-CD at each intestinal segment. By measuring the permeability results of Lucifer yellow, we propose that the increased permeability across intestinal membrane by HP-beta-CD plays an important role in enhanced TS absorption. Meanwhile, the morphological studies using HP-beta-CD did not reveal significant tissue damage in any of the intestinal segments. The results obtained support the use of HP-beta-CD to improve the gastrointestinal tract absorption of TS.
Wang
Ling
L
Department of Clinical Pharmacy, Key Laboratory of Drug Targeting of the Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
Lai
Yan
Y
Li
Chenrui
C
Jiang
Xuehua
X
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D045784:Abietanes; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D005612:Freeze Drying; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D010539:Permeability; D010616:Phenanthrenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
D045784:Abietanes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D010616:Phenanthrenes; D047392:beta-Cyclodextrins; C021751:tanshinone; D000073738:2-Hydroxypropyl-beta-cyclodextrin