Current status of selected oral peptide technologies in advanced preclinical development and in clinical trials.

The development of oral dosage forms that allows absorption of therapeutic peptides to the systemic circulation is one of the greatest challenges for the pharmaceutical industry. Currently, a number of technologies including either mixtures of penetration enhancers or protease inhibitors and/or nanotechnology-based products are under clinical development. Typically, these formulations are presented in the form of enteric-coated tablets or capsules. Systems undergoing preclinical investigation include further advances in nanotechnology, including intestinal microneedle patches, as well as their combination with regional delivery to the colon. This review critically examines four selected promising oral peptide technologies at preclinical stage and the twelve that have progressed to clinical trials, as indicated in www.clinicaltrials.gov. We examined these technologies under the criteria of peptide selection, formulation design, system components and excipients, intestinal mechanism of action, efficacy in man, and safety issues. The conclusion is that most of the technologies in clinical trials are incremental rather than paradigm-shifting and that even the more clinically advanced oral peptide drugs examples of oral bioavailability appear to yield oral bioavailability values of only 1-2% and are, therefore, only currently suitable for a limited range of peptides.

Glucomannan, a promising polysaccharide for biopharmaceutical purposes.

Over the last few decades, polysaccharides have gained increasing attention in the biomedical and drug delivery fields. Among them, glucomannan (GM), has become a particularly attractive polymer. In this paper, we review the physicochemical and biological properties which are decisive for the exploitation of GM as a biomaterial. These properties include the structural organization, molecular weight, solubility, viscosity, gelling properties and degradation behavior. Moreover, herein we analyze the possibilities of combining GM with other hydrophilic polymers, as well as the preparation of semisynthetic derivatives of GM, which may be of interest in the pharmaceutical context. Finally, we discuss the specific applications of GM in the drug delivery field.