In recent decades, drug-loaded carrier systems have become a viable option to replace or augment current, unsuccessful therapies that address a myriad of disease conditions. In this area, a successful therapy needs to address the following parameters: specificity, long circulation, biocompatibility/biodegradability, desired pharmacokinetics of single & multiple therapeutics, carrier-cell interactions, and potential imaging capabilities. While various formulations have tackled some of these characteristics, a concrete methodology to design multifunctional particles addressing all parameters is currently lacking.
Herein, the method of electrohydrodynamic (EHD) co-jetting and downstream processing are used to design multifunctional particles with tunable characteristics that could be used to address all desired parameters. Specifically, each of the chapters address (i) the development of carriers with selective and orthogonal surface modifications using functional polymers incorporated into individual compartments for the addition of stealth, targeting, or therapeutic capabilities; (ii) the development of carriers with programmable physical properties such as shape, size, porosity, roughness, and charge that can determine the fate of a particle in the body, and the testing of nanoparticles in animal models to determine their biodistribution; (iii) the development of particles with complex degradation and release kinetics of therapeutics using rapidly degrading or stimuli-responsive (pH, light, & oxidative stress) polymers; (iv) the design of multifunctional particles loaded with multiple therapeutics for cochlear delivery and their testing to determine the therapeutics’ release kinetics, the particles’ persistence & biodistribution in the cochlea, and the general biocompatibility of the system. Accordingly, this dissertation suggests the potential establishment of a toolbox that can be used for the design of particles with programmable properties for individual applications in the effective delivery of therapeutics.PhDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111636/1/rahmani_1.pd
