ABSTRACT
Today, most biopharmaceuticals are administered parenterally. Their oral bioavailability is negligible, due to poor absorption and rapid and extensive degradation in the gastrointestinal tract. Limited absorption stems mostly from their large molecular size (typically >1000 Da) and, in most cases, also from their low lipophilicity, which limits permeability across the gastrointestinal epithelium (1,2). In spite of these inherent diffi culties, the development of oral biopharmaceuticals has been pursued for decades, since the discovery of the fi rst biopharmaceuticals, insulin and heparin, nearly a century ago. Efforts were abandoned after initial limited success; however, the advent of biotechnology and the proliferation of biopharmaceuticals over the past two decades have led to a renewed interest in developing oral forms of peptides and proteins. A number of approaches have been explored, including coadministration with enzyme inhibitors, use of permeation enhancers, and encapsulation in nano-and microparticles (3-7). Some approaches have been abandoned and, to date, only few have shown commercial viability and progressed to clinical studies (8). Success factors in developing viable oral biopharmaceuticals vary from drug to drug but overall include reasonable bioavailability and variability, stability of fi nal product, acceptable cost of goods and manufacturing, and limited side effects and toxicity.
