BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 Lecture 15: Stealth' particles Last time Nano- and micro-particle carriers Today Delivery of drugs to tissue from circulation stealth particles theory and function Reading S. Stolnik et al. 'Long circulating microparticulate drug carriers, Adv. Drug. Deliv. Rev 16,195(1995) Delivery of drugs to tissues via systemic circulation Avenues of systemic molecule delivery 1. Intravenous injection 2. oral delivery to lumen of gut ary according to the specific type of receptor (1) Most receptors return Transcytosis brane domain from which they came; (2) some recep- mes, where they are degraded; and (3)some recepto uutmain of the plasma membrane, thereby mediating Figure 13-32 Possible fates for transmembrane receptor proteins that objectives for systemic delivery to tissues/organs avoid premature elimination by kidneys o kidneys filter out molecules smaller than X nm Avoiding reticuloendothelial system(RES) o Particles larger than 200 nm screened by monocytes and macrophages in liver and spleen(Biochem Biophys Res Commun. 177, 861(1991)) upffer cells- macrophages in liver o Particulate removal aided by process of opsonization Process of tagging' foreign particles for efficient removal by macrophages Lecture 15-stealth' particles 1 of 8BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 15 – ‘stealth’ particles 1 of 8 Lecture 15: ‘Stealth’ particles Last time: Nano- and micro-particle carriers Today: Delivery of drugs to tissue from circulation ‘stealth’ particles theory and function Reading: S. Stolnik et al. ‘Long circulating microparticulate drug carriers,’ Adv. Drug. Deliv. Rev. 16, 195 (1995) Delivery of drugs to tissues via systemic circulation Avenues of systemic molecule delivery 1. Intravenous injection 2. oral delivery to lumen of gut Transcytosis: objectives for systemic delivery to tissues/organs ƒ avoid premature elimination by kidneys o kidneys filter out molecules smaller than X nm ƒ Avoiding reticuloendothelial system (RES) o Particles larger than 200 nm screened by monocytes and macrophages in liver and spleen (Biochem. Biophys. Res. Commun. 177, 861 (1991)) ƒ Kupffer cells – macrophages in liver o Particulate removal aided by process of opsonization ƒ Process of ‘tagging’ foreign particles for efficient removal by macrophages