Transport of leuprolide across rat intestines, rabbit intestine and caco-2 cell monolayer

Guo, J., Ping, Q., Jiang, G., Dong, J., Qi, S., Feng, L., Li, Z. and Li, C. (2004) Transport of leuprolide across rat intestines, rabbit intestine and caco-2 cell monolayer. International Journal of Pharmaceutics, 278 (2). pp. 415-422. ISSN 0378-5173

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Abstract

The purpose of this study was to investigate the transport mechanisms and causes of low bioavailability of leuprolide. The everted gut sac technique and Caco-2 cell monolayer were used to examine: (1) transport properties, enzyme degradation and apparent permeation coefficient (Papp); (2) the influence of trypsin inhibitor, EDTA, chitosan and alginate on drug transport; and (3) the effect of animal species on the intestinal transport. Results showed flux increased with increasing concentration of drug, showing a passive diffusion pathway. The enzyme degradation in rabbit gut was the highest. The Papp of (4.19 ± 1.33) × 10−5 cm/s in rat gut was the largest and the Papp of (5.20 ± 0.20) × 10−7 cm/s in Caco-2 cell the smallest. At a low concentration of drug, trypsin inhibitor had strong enhancement effect on the Papp by protecting enough drug for permeation. Chitosan had no effect on the activity of α-chymotrypsin. The increase in Papp was due to opening of the tight junctions and interaction with cells. In conclusion, both inhibition of proteolytic enzymes and opening the tight junctions to allow for paracellular transport improved the intestinal absorption. At low drug concentration, reduction of enzyme degradation is the most important factor.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups:	Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter Faculty of Science > Research Groups > Drug Delivery and Pharmaceutical Materials (former - to 2017)
Depositing User:	Pure Connector
Date Deposited:	09 Mar 2015 07:36
Last Modified:	28 Mar 2025 06:29
URI:	https://ueaeprints.uea.ac.uk/id/eprint/52553
DOI:	10.1016/j.ijpharm.2004.03.031

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