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Polymer colon drug delivery systems and their application to peptides, proteins, and nucleic acids

  • Review Article
  • Published:
American Journal of Drug Delivery

Abstract

Most therapeutic peptides and proteins are administered via the parenteral route, which presents numerous drawbacks and limitations. To overcome these drawbacks, alternative administration routes, such as oral or mucosal routes, have been investigated. The oral route presents a series of attractive advantages for the administration of therapeutic compounds, such as the avoidance of the pain and discomfort associated with injections, good patient compliance, and being less expensive to produce. However, oral administration of peptides, proteins, or nucleic acids also presents several difficulties because of their instability in the upper gastrointestinal (GI) tract and their poor transport across biologic membranes. Among the various approaches developed to improve the oral delivery of peptides, proteins, or nucleic acids, specific delivery to the colon has attracted a lot of interest because of its potential for the local treatment of colonic diseases, systemic delivery of poorly absorbed drugs, and vaccine delivery. Numerous pharmaceutical approaches described in this review have been exploited for the development of colon-targeted drug delivery systems using various concepts, such as pH-dependent, time-dependent, pressure-controlled, or bacterially triggered delivery systems. The action of the pH-dependent delivery systems is based on pH differences between the stomach and the ileum. Time-dependent delivery systems are based on the transit time of pharmaceutical dosage forms in the GI tract, drug release being delayed until they reach the colon. A combination of pH- and time-dependent delivery systems has also been described to avoid the drawbacks of both strategies. The pressure-controlled delivery concept exploits the physiologic luminal pressure of the colon as the driving force for site-specific delivery of drugs. Finally, bacterially triggered delivery systems exploit the enormous diversity of enzymatic activity associated with the colonic microflora. Bacterially triggered delivery systems are generally composed of polymers, which are specifically degraded by colonic enzymes of microbial origin. These polymers have been used to form prodrugs with the drug moiety, as coating materials for the drug core, or as embedding media to entrap the drug into matrix or hydrogel systems. Each of these concepts has advantages and limitations. They present varied colonic specificity and, among them, bacterially triggered delivery systems in particular show the greatest potential for colonic delivery of peptides, proteins, and nucleic acids.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgments

The authors would like to acknowledge the French Ministery of Research for supporting the fellowship of Sandrine Bourgeois. The authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. School of Pharmacy, Paris-Sud University, Châtenay-Malabry Cedex, France

    Sandrine Bourgeois, Richard Harvey &  Elias Fattal

  2. Department of Pharmacy, King’s College London, London, UK

    Richard Harvey

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  1. Sandrine Bourgeois
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Bourgeois, S., Harvey, R. & Fattal, E. Polymer colon drug delivery systems and their application to peptides, proteins, and nucleic acids. Am J Drug Deliv 3, 171–204 (2005). https://doi.org/10.2165/00137696-200503030-00003

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