Colon-specific drug delivery systems based on cyclodextrin prodrugs: in vivo evaluation of 5-aminosalicylic acid from its cyclodextrin conjugates.
OBJECTIVE
To investigate the release of cyclodextrin-5-aminosalicylic acid (CyD-5-ASA) in cecum and colon.


METHODS
An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of alpha-, beta- and gamma-cyclodextrins (CyDs) through an ester linkage, and the in vivo drug release behavior of these prodrugs in rat's gastrointestinal tract after the oral administration was investigated.


RESULTS
The 5-ASA concentration in the rat's stomach and small intestine after the oral administration of CyD-5-ASA conjugate was much lower than that after the oral administration of 5-ASA alone. The lower concentration was attributable to the passage of the conjugate through the stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specific in the cecum and colon. The oral administration of CyD-5-ASA resulted in lower plasma and urine concentration of 5-ASA than that of 5-ASA alone.


CONCLUSIONS
CyD-5-ASA conjugates may be used as prodrugs for colon-specific drug delivery system.
Zou
Mei-Juan
MJ
School of Pharmacy, Shenyang Pharmaceutical University, Shenhe District, Shenyang 110016, Liaoning Province, China.
Cheng
Gang
G
Okamoto
Hirokazu
H
Hao
Xiu-Hua
XH
An
Feng
F
Cui
Fu-De
FD
Danjo
Kazumi
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D003106:Colon; D003505:Cyclodextrins / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D007408:Intestinal Absorption; D008297:Male; D019804:Mesalamine / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D011355:Prodrugs; D019804:Mesalamine