Past, present, and future technologies for oral delivery of therapeutic proteins

Biological drugs are usually complex proteins and cannot be orally delivered due to problems related to degradation in the acidic and protease-rich environment of the gastrointestinal (GI) tract. The high molecular weight of these drugs often results in poor absorption into the periphery when administered orally. The most common route of administration for these therapeutic proteins is injection. Most of these proteins have short serum half-lives and need to be administered frequently or in high doses to be effective. So, difficulties in the administration of protein-based drugs provides the motivation for developing drug delivery systems (DDSs) capable of maintaining therapeutic drug levels without side effects as well as traversing the deleterious mucosal environment. Employing a polymer as an entrapment matrix is a common feature among the different types of systems currently being pursued for protein delivery. Protein release from these matrices can occur through various mechanisms, such as diffusion through or erosion of the polymer matrix, and sometimes a combination of both. Encapsulation of proteins in liposomes has also been a widely investigated technology for protein delivery. All of these systems have merit and our worthy of pursuit. (C) 2007 Wiley-Liss, Inc.