NER: Continuous Flow Induced Phase Inversion: a New Method for Manufacturing Drug Delivery Biopolymer Nanoparticles

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This project proposes to explore the feasibility of using a recently developed technique, Flow Induced Phase Inversion (FIPI), for continuous manufacturing of nanoparticles made of poly(DL-lactic-co-glycolic acid) containing bovine serum albumin as a model drug. The specific aims of this project are (i) to examine systematically the phase inversion properties of combinations of biocompatible polymers, surfactant, and solvents. (ii) To implement an experimental continuous flow system where the effects of material properties, mixing geometry, and operating conditions on FIPI can be examined. (iii) to develop a theoretical understanding of the effects of hydrodynamics, surface tension, and rheology on the fundamental FIPI physics. An experimental apparatus will be implemented to examine phase-inversion behavior. The polymer will be dispersed in a solvent and then mixed with predetermined amounts of a non-solvent to form a dispersion where the polymer solution is the continuous phase. Subsequently, very high rates of hydrodynamic deformation will be applied to elicit phase inversion, transforming the viscous polymer solution into a nanodispersed phase. The resulting droplets will be hardened by solvent extraction. After the process has been characterized in a customized rheometer, this information will be used to develop continuous in-line process equipment. Success will be determined based on the size, the amount, and the ease of manufacturing of bioparticles. This project will advance the understanding of phase inversion phenomena in general and of FIPI in particular. The main intellectual merit will be to confirm the working hypothesis that FIPI can be used to make biodegradable drug nanoparticles. The proposed work is expected to have substantial impact. Since many drugs currently fail during development due to poor dissolution properties, the development of suitable approaches for enhancing dissolution and bioavailability can breathe new life into many "dead" compounds, i.e., initially promising molecules that have been discarded by pharmaceutical companies. In addition, educational components will include laboratory demonstrations and outreach to industry.