Validation of a pharmacokinetic model of colon-specific drug delivery and the therapeutic effects of chitosan capsules containing 5-aminosalicylic acid on 2,4,6-trinitrobenzenesulphonic acid-induced colitis in rats
H. Tozaki et al., Validation of a pharmacokinetic model of colon-specific drug delivery and the therapeutic effects of chitosan capsules containing 5-aminosalicylic acid on 2,4,6-trinitrobenzenesulphonic acid-induced colitis in rats, J PHARM PHA, 51(10), 1999, pp. 1107-1112
A pharmacokinetic model of colon-specific drug delivery developed in a prev
ious study has been validated by use of 5-aminosalicylic acid (5-ASA) as a
model anti-inflammatory drug.
The simulation curves obtained from the pharmacokinetic model were in good
agreement with experimental data obtained after oral administration of 5-AS
A-containing chitosan capsules. The concentrations of 5-ASA in the large in
testinal mucosa after drug administration were higher than after administra
tion of the drug in carmellose suspension. We then attempted colon-specific
delivery of an anti-ulcerative colitis drug, in chitosan capsules, to acce
lerate healing of 2,4,6-trinitrobenzenesulphonic acid sodium salt (TNBS)-in
duced colitis in rats. To confirm this therapeutic model, salazosulphapyrid
ine (SASP), a commercially available 5-ASA prodrug, was used as positive co
ntrol. Colonic injury and inflammation were assessed by measuring myelopero
xidase activity and visual assessment (damage score), respectively. Because
SASP is effective against TNBS-induced colitis in rats, use of the SASP-se
nsitive TNBS-induced colitis model validated the therapeutic effects of 5-A
SA-containing chitosan capsules, which were significantly better than those
of a suspension of the drug in carmellose.
These findings suggest that our pharmacokinetic model of colon-specific dru
g delivery can accurately evaluate this colon-specific delivery system and
that 5-ASA-containing chitosan capsules are more effective than other 5-ASA
formulations for treatment of TNBS-induced colitis in rats.