Polymers for delivering peptides and proteins

Abstract

The use of polymers for delivering peptide and protein drugs is described. Soluble-polymer technology attempts to bind a polymer to all sites on therapeutic protein molecules that cause the body to recognize the molecules as foreign. Goals include a stable linkage, water solubility, low immunogenicity, prolonged half-life, and intact biological activity. Polyethylene glycol (PEG)-adenosine deaminase (ADA), or pegademase bovine, has FDA-approved labeling as replacement therapy for ADA deficiency in patients with severe combined immunodeficiency disease who are not suitable candidates for bone marrow transplantation. Pegademase bovine reverses the toxic accumulation of adenosine and deoxyadenosine in adenosine deaminase-deficient cells, restoring the immune system. PEG-asparaginase (pegaspargase) has shown promise in patients with acute lymphocytic leukemia; allergic reactions have been minimal. Animal studies suggest that superoxide dismutase has potential use in conditions in which the body's ability to remove oxygen free radicals is reduced, such as burns and myocardial infarction; coupling with PEG may greatly increase the protein's half-life. Other PEG-conjugated proteins under investigation include PEG-catalase, PEG-uricase, PEG-honeybee venom, PEG-hemoglobin, and PEG-modified ragweed pollen extract. Dextran, albumin, DL-amino acids, and polyvinyl pyrrolidone have also been studied as protein carriers; most of the products created thus far have not shown much promise. The coupling of polymers to proteins has yielded protein drugs with intact biological activity and reduced immunogenicity, but much remains to be learned about this technology.