Proteins as Drugs: Analysis, Formulation and Delivery

The use of proteins as drugs is by no means new. Insulin, gamma-globulin and protein-containing vaccines have been routinely employed for decades. However, the advent of recombinant DNA technology has resulted in a dramatic expansion of interest in their pharmaceutical applications. It now appears that we can make virtually any desired protein in sufficient quantities for therapeutic use, although often with significant difficulty. It is considerably more problematic, however, to take the appropriate macromolecule and prepare it as a clinically acceptable drug substance. This problem arises from several sources. First, proteins are intrinsically less stable than their lower molecular weight (MW) pharmaceutical counterparts. Although this has turned out to be less of a problem than first anticipated, it remains a continuing challenge to formulate proteins that can be handled without damage throughout their entire lives; from their initial preparation, through distribution within the complex bio-medical system, into their ultimate clinical use in a hospital or doctor’s office or perhaps even in the home. Second, to make optimum use of a protein as a pharmaceutical agent, it is necessary to get it to the relevant in vivo site of action with maximum efficiency. A major potential power of proteins as therapeutic agents resides in their intrinsic compatibility with living systems. As critical components of virtually all biochemical processes, the presentation of a natural protein or one with specifically altered functional properties offers the opportunity to intervene in a pathological process with a high degree of specificity and minimal perturbation of normal processes.