A time to every purpose: Reaction-based approaches to biological interactions of pegylated vesicles and worm micelles
The circulation times of nanoparticles range from a few hours to a few days. The variations in the kinetics from particle to particle are due to a range of parameters, including their adhesiveness, resistance to opsonization, and hydrodynamics. In this thesis, we examine a novel vesicle system, the polymersome, and use its circulation dynamics to deconstruct the process by which particles are cleared from the system. We then construct a model that can reflect the data available for diverse systems, including polymeric worm micelles. The model, in turn, can be used to justify the combination of the polymersome data with the cannon of liposome data available, from which we can construct trends for circulation times in terms of vesicle properties, namely PEG brush density, length, and vesicle size. We also use the model to determine relevant biological factors, such as the implication of a “Marker of Self” protein. Using the vesicle system, we determine the local forces involved in capture and uptake of vesicles. Finally, we demonstrate the importance of a PEG brush in release as a stabilizer of pores in membranes. With a truly controlled circulation times, we show that it then is possible to construct drug-vesicle combinations that can dampen the peaks and valleys in drug concentrations seen with traditional drugs.
Chemical engineering|Biomedical research|Biophysics
Photos, Peter Joseph, "A time to every purpose: Reaction-based approaches to biological interactions of pegylated vesicles and worm micelles" (2004). Dissertations available from ProQuest. AAI3152089.