The rationale for peptide drug delivery to the colon and the potential of polymeric carriers as effective tools

Abraham Rubinstein*, Boaz Tirosh, Muhammad Baluom, Taher Nassar, Ayelet David, Raphael Radai, Irit Gliko-Kabir, Michael Friedman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


The explicit use of colon-specific drug delivery systems is for the local treatment of colon diseases such as ulcerative colitis. Some efficient therapeutic systems, primarily prodrugs and polymeric carriers of salicylate derivatives, have been developed and commercialized during the past 20 years. Speculating that the colon is a superior organ for peptide drug absorption after oral ingestion, many studies indicate that colon-specific drug carriers may potentially be used for the delivery of peptide drugs to that organ. This notion stems from the assumption that the overall proteolytic activity in the colon is lower than and different from the proteolytic activity in the small intestine. For example, it has been found that the degradation rate of albumin, azoalbumin casein, azocasein and collagen in human ileal effluent was faster than the degradation rate in fecal slurries. Other studies, in which the degradation rates of insulin and insulin B-chain in the small and large intestine of the guinea pig were compared, showed higher degradation rates in the small intestine. It is noteworthy, however, that a peptide drug may stay much longer (up to ten times longer) in the large intestine. Thus, even if the enzymic activity is lower, the drug is exposed longer to proteolytic activity. Yet, if the drug is properly protected or formulated with absorption enhancers, the prolonged residence time may increase drug absorption from the large intestine. Thus, prolonged drug blood levels of the ACE inhibitors benazepril and captopril have been demonstrated in a number of studies after colonic administration to rats and dogs. A possible explanation for the 'flat' pharmacokinetic profiles obtained may be the 'closed compartment conditions' existing in the colon resulting from the extremely slow propulsive movement of digesta in that organ. These almost stationary conditions may also benefit the performance of functional adjuvants, such as absorption enhancers or peptidase inhibitors, because their dilution rate with the luminal contents of the colon is low. For the purpose of colon-specific drug delivery a variety of polymers has been developed, including acrylic polymers modified with azo cross-linkers and saccharidic polymers. Both kinds have been tested in vitro and in animal studies for their ability to be degraded specifically by typical enzymes of the colon. In addition, swellable polymers were utilized in new pulsatile and delayed-release colonic delivery systems after being protected with enteric coating polymers. To secure peptide drugs in the GI tract, especially in the colon, the use of cross-linked acrylic acid derivatives such as polycarbophil and carbopol® 934 has also been suggested. In conclusion, new biodegradable polymers and polymers with controllable swelling properties can be used for the specific delivery of drugs to the colon. Furthermore, some polymers, by virtue of their intrinsic proteolytic inhibition properties, could be used to improve the absorption of peptide drugs from colonic delivery systems.

Original languageAmerican English
Pages (from-to)59-73
Number of pages15
JournalJournal of Controlled Release
Issue number1-2
StatePublished - 5 May 1997

Bibliographical note

Funding Information:
Part of the work cited in this manuscript was supported by (a) a research grant (no. 4550) from the Joint Research Center of the EC Commission for Science and R&D and the Israeli Ministry of Science and Art, (b) a research grant from Perio Products Ltd. Jerusalem, Israel. The following individuals were also involved in past studies: A. Sintov, D. Nakar and S. Ankol.


  • Colon
  • Peptide drug delivery
  • Polymeric carriers


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