BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 Function of stealth particles o PEGylated molecules o PEGylated IFN-o2a Treatment of Hepatitis C- has antiviral activity(induces macrophages to kill virus) o PEGylated interleukin-6 100-fold increase in blood half life with pegylation thrombopoietic potency increased 500-fold Table 1 Influence of pegylation on pharmacokinetics and phar Pharmacokinetic effect Pharmacodynamic effect Interferon-a2a Sustained absorption In wio antiviral activity increased 12-to 135-times Increased half-life(from 3-8 h to 65 h) Antitumour activity increased 18-fold Decreased volume of distribution (from 31-73I to 8-12) mproved sustained response to chronic hepatitis C urEase systemic ch aI e(run 6.6-29.2 L008-0.10 Mi Interleukin-6 Increased half-life(rom 2. 1-206 min) Thrombopoietic potency ncreased 500-times Tumour necrosis factor Increased hali-life(tom 3 to 45-136min) Antitumour potency increased 4-to 100-times b三之出导 s injected every other day and its short ifetme in circulation leads to pulsed blood concentratons levelswhich cycle bebw level. The branched PEG40KDa IFN-a2a has a lng circulating ifetme due to the presence of the PEg, and the once weekly injection leads constant bod concentrations above the herapeutic level over the one-week penod aris,2003) PEGylated microspheres Li et al. showed significant increases in circulation time by preparing controlled release microparticles using PEG-PLGaA block copolymers o Formation of microspheres by double emulsion process Block copolymer self-emulsifies and PEG coats both internal and external aqueous interfaces Benefit of improved protein stability within microspheres? Lecture15-‘ stealth’ particles 5 of 8BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 15 – ‘stealth’ particles 5 of 8 Function of stealth particles o PEGylated molecules o PEGylated IFN-α2a4 ƒ Treatment of Hepatitis C- has antiviral activity (induces macrophages to kill virus) o PEGylated interleukin-6 ƒ 100-fold increase in blood half life with pegylation ƒ thrombopoietic potencty increased 500-fold (Harris, 2003) ƒ PEGylated microspheres: ƒ Li et al. showed significant increases in circulation time by preparing controlled release microparticles using PEG-PLGA block copolymers2 o Formation of microspheres by double emulsion process ƒ Block copolymer self-emulsifies and PEG coats both internal and external aqueous interfaces • Benefit of improved protein stability within microspheres?