EAGER: Preliminary Study on Novel self-assembled Toroidal-Spiral MicroParticles (TSMPs) for sustained release of therapeutic proteins and peptides: theory and experiments

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The research objective of the proposal is to test the hypothesis that self-assembly by interaction of viscous sedimentation, diffusion, and cross-linking kinetics can produce a new category of polymeric micro-particles with a toroidal-spiral internal structure that offers advantages for sustained drug release. More specifically, during the particle formation, therapeutic proteins and peptides are simultaneously encapsulated into the toroidal-spiral channels. In contrast with prevailing protein delivery methods, toroidal-spiral micro-particles(TSMPs) can be formed and loaded with proteins entirely within the aqueous phase, under benign conditions (room temperature, low shear and low interfacial tensions) that preserve delicate macromolecular conformations and thereby maximize bioactivity and bioavailability. To validate this novel idea, and thereby mitigate conceptual risk for the longer project, we request support for one-year of research to provide more preliminary results for a regular proposal in future. Within the one-year period proposed here, two key aspects will be addressed: (1) protein self-loading into the toroidal-spiral particles, and (2) scaling down toroidal-spiral particles from the millimeter scale (currently achievable) to micron dimensions. On the basis of preliminary experimental and theoretical work, we expect success in both endeavors. The research plan below includes contingency plans in case the initial approach does not work as anticipated. Intellectual Merit. Integrating laboratory investigation with versatile computer simulations, this proposal addresses the fundamental fluid mechanics and mass transfer that enable a new category of polymeric drug-delivery particles for local sustained release of therapeutic proteins and peptides. TSMPs will be generated by light-triggered flash polymerization of intricately wound liquid structures. These liquid structures form by hydrodynamic forces when a water-miscible, polymeric drop sediments at low Reynolds number through an aqueous solution. The initial impact of the polymeric droplets into the aqueous pool (forming bell shapes of vortex rings) for arbitrary viscosity ratio and non-Newtonian rheology represents a largely unexplored regime in fluid mechanics, to which both quantitative visualization experiments and computer modeling will be applied. The anticipated findings will greatly enhance our quantitative understanding of new self-assembly processes, thereby providing a quantum leap in producing microparticles with novel structures. Broader Impacts. This project provides a technological platform that can potentially be translated into medical treatments for many complex diseases. Research will impact the ChE curriculum through a new graduate microfluidics course, two modules for the undergraduate Transport Phenomena sequence and a sequence of undergraduate research projects. A dedicated website (www.microfluidtech.org) will publish a suite of Java-based educational modules designed for college and pre-college students, also to be described in an educational journal article. The highly visual nature of the experiments and theoretical results, as well as the societal relevance of the biomedical applications, represent a natural draw for students being recruited into chemical engineering through ongoing departmental relationships with Chicago land high schools. This project leverages ongoing outreach, recruitment and retention efforts by Liu and Nitsche among women and underrepresented minority students.