Lack of effect of beta-cyclodextrin and its water-soluble derivatives on in vitro drug transport across rat intestinal epithelium.
The present study aimed to investigate whether beta-cyclodetxrin (beta-CD) and its water-soluble derivatives, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and sulfobutyl ether beta-cyclodextrin (SBE-beta-CD), exert any effects on the permeation of two drug transport markers (propranolol and lucifer yellow) across rat intestinal epithelium. Rat ileum was stripped of its serosa and mounted inside an Ussing Chamber. Apparent permeability coefficients (P(app)) of the markers from the mucosal to serosal side of the tissue were determined at 37 degrees C in the presence and absence of the beta-cyclodextrins on the mucosal side. Potential difference (PD) was constantly monitored during each experiment to ensure maintenance of the viability and integrity of the tissue. Pre-incubation with 1% beta-CD, 1% HP-beta-CD or 1.48% SBE-beta-CD on the mucosal side for 30 min did not significantly alter the PD and the propranolol permeability (p>0.05). Co-incubation with 1% beta-CD or 1% HP-beta-CD exerted no significant effect on the P(app) of both propranolol and lucifer yellow (p>0.05), but co-incubation with 1.48% SBE-beta-CD lowered the P(app) of propranolol from (1.71+/-0.44)x10(-5) to (0.19+/-0.04)x10(-5)cm/s, which may be ascribed to the molecular complexation of propranolol with SBE-beta-CD. All three beta-cyclodextrins exert no apparent impact on both (passive) transcellar and paracellular drug transports.
Zheng
Ying
Y
School of Pharmacy, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
Zuo
Zhong
Z
Chow
Albert H L
AH
D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D015194:Diffusion Chambers, Culture; D004337:Drug Carriers; D005456:Fluorescent Dyes / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007546:Isoquinolines / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D010539:Permeability; D011433:Propranolol / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D004337:Drug Carriers; D005456:Fluorescent Dyes; D007546:Isoquinolines; D047392:beta-Cyclodextrins; D014867:Water; C017475:lucifer yellow; D011433:Propranolol