Strategies for delivery of peptides utilizing absorption-enhancing agents

The development of oral formulations for the effective delivery of peptides and proteins has been an elusive target. Although some success has been achieved (e.g., with cyclosporine), progress has been slow compared with what has been achieved with more traditional, organic drug molecules. Poor membrane permeability, enzymatic instability, and large molecular size are three factors that have remained major hurdles for peptide formulators. Absorption-enhancing agents that have been effective, at least in research environments, with smaller drug candidates, have also shown some limited efficacy in small animal models with certain peptides. In most cases, however, effective formulations have only achieved fairly low peptide absorption (< 10%) and have also resulted in significant alterations in the normal cellular morphology of the gastrointestinal tract, at least on a transient basis. Both literature and current data are reviewed in this report. Taken as a whole, the data suggest that the successful development of oral peptide formulations remains a significant challenge. Where successes are achieved, they will most likely be on a case-by-case basis and will reflect a balance between absorption-promoting efficacy of the formulation and the extent to which transient alteration of cell or tissue morphology occurs.