The Origins and Evolution of Controlled Drug Delivery
Systems Using Biomaterials
■ Date: 2017. 03. 22(Wed), 12:30 ~
■ Place: Auditorium (1F) at POSTECH Biotech Center (생명공학센터, 1층 대강당(182호)
(Time and venue changed)
■ Speaker: Prof. Allan Hoffman (University of Washington)
■ Host of a Seminar: Prof. Sei Kwang Hahn
※ Speaker Language: ENGLISH
The idea to conjugate PEG [poly(ethyleneglycol)] to a protein, i.e., to “PEGylate” a protein, was first proposed by Prof. Frank Davis (Rutgers Univ.) in the late 1960s-early 1970s. (1) He wanted to make the new recombinant proteins less immunogenic in our bodies, and thereby enhance their circulation and activity lifetimes. He thought that if he could conjugate a hydrophilic polymer to the “new” protein, it might not be recognized by the immune system as a foreign molecule. Davis further said that he discovered mPEG (methoxy-PEG) in a “company catalog”, and he proposed to conjugate the one, reactive –PEG-OH end group to the protein. He asked his PhD student, Abraham Abuchowski, to work on it. Abuchowski chose an enzyme, bovine liver catalase, as his model protein. He subsequently found that the PEGylated protein did indeed have reduced immunogenicity, along with a longer circulation lifetime. They published their results in J Biol Chem in 1977 and they continued to actively publish articles on PEGylated proteins (e.g., 2). In 1981 Abuchowski founded the first “PEGylation” company, which he and colleagues called Enzon®, to make and sell PEGylated proteins to pharmaceutical companies. Abuchowski was the founding President and CEO of Enzon. Frank Davis was an Advisor to Enzon and later, after he retired, he became a Vice President of Enzon.
Meanwhile, in the 1970s others were interested in “biocompatible” biomaterials that would be used in contact with body fluids such as blood. Prof. Edward W. Merrill in the Chemical Engineering Dept. at MIT was preparing lightly crosslinked hydrogels of PEO, and he published a seminal article in 1983 entitled “Polyethylene Oxide as a Biomaterial”, in which he said: “Cumulative evidence indicates a very low level of interaction between polyethylene oxide and biological species studied (molecular, cellular). Thus this polymer is potentially important as a biomaterial”. (3)
This talk will review this early history of PEGylation, and will also describe the latest findings and current state of the art of PEGylation of drugs and biomaterial surfaces.
References: (1) F.F. Davis, ADDR, 54 (2002) 457-458
(2) A. Abuchowski, J Biol Chem, 252 (1977) 3578-3581
(3) E.W. Merrill, ASAIO J, 6, (1983) 60
Dept. of MSE / CITE / BK21+