BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Opsonization B cell B cells binding to a foreign protein, drug, or particle can be triggered to produce antibodies against the drug or carrier Resta loM:lc° Figure 9-11 Functions of cytokines in B cell growth and differentiation argeted delivery to select tissues, cells Molecular carriers Role of polymeric carriers 1. Multivalency High avidity binding to low-affinity receptors for detection/delivery CD40-dextran conjugate example Potent delivery on per-molecule basis 1 carrier delivered 10-50 drug molecules delivered 2. penetration of tissues 3.'stealth functions Chemistry and physical chemistry of conjugation non-covalent linkages Molecular size considerations Micelle carriers Amphiphilic block copolymer structures form micelles in water o Monodisperse copolymers can form relatively monodisperse micelle spheres o Compartmentalization/association of cargo within the micelle ocalization driven by hydrophilic/hydrophobic balance Hydrophobic core-hydrophobic drug Hydrophilic drugs -only associate with corona Amphiphilic drugs- localized at core-corona interface Lecture 14-nano- and micro-particles 3 of 6BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Opsonization: QuickTime™ and a GIF decompressor are needed to see this picture. B cells binding to a foreign protein, drug, or particle can be triggered to produce antibodies against the drug or carrier: ƒ targeted delivery to select tissues, cells Molecular Carriers Role of polymeric carriers 1. Multivalency ƒ High avidity binding to low-affinity receptors for detection/delivery x CD40-dextran conjugate example ƒ Potent delivery on per-molecule basis x 1 carrier delivered = 10-50 drug molecules delivered 2. penetration of tissues 3. ‘stealth’ functions Chemistry and physical chemistry of conjugation ƒ non-covalent linkages o Ni-histadine linkages ƒ Molecular size considerations 3 Micelle Carriers ƒ Amphiphilic block copolymer structures form micelles in water o Monodisperse copolymers can form relatively monodisperse micelle spheres o Compartmentalization/association of cargo within the micelle 3 ƒ Electrostatic interactions 4 ƒ Localization driven by hydrophilic/hydrophobic balance x Hydrophobic core-hydrophobic drug x Hydrophilic drugs – only associate with corona x Amphiphilic drugs – localized at core-corona interface Lecture 14 – nano- and micro-particles 3 of 6