STRATEGIES FOR DELIVERY OF PEPTIDES UTILIZING ABSORPTION-ENHANCING AGENTS

The development of oral formulations for the effective delivery of pep tides and proteins has been an elusive target. Although some success h as been achieved (e.g., with cyclosporine), progress has been slow com pared with what has been achieved with more traditional, organic drug molecules. Poor membrane permeability, enzymatic instability, and larg e molecular size are three factors that have remained major hurdles fo r peptide formulators. Absorption-enhancing agents that have been effe ctive, at least in research environments, with smaller drug candidates , have also shown some limited efficacy in small animal models with ce rtain peptides. In most cases, however, effective formulations have on ly achieved fairly low peptide absorption (<10%) and have also resulte d 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 d ata suggest that the successful development of oral peptide formulatio ns remains a significant challenge. Where successes are achieved, they will most likely be on a case-by-case basis and will reflect a balanc e between absorption-promoting efficacy of the formulation and the ext ent to which transient alteration of cell or tissue morphology occurs.