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Design and fabrication of solvent compatible polymer microfluidic chips and its application to particle production and drug delivery

University of British Columbia

Despite the recent advancements in the field of microfluidics, the potential of rapid development is often limited due to the inherent challenges posed by the materials used for microfluidic device fabrication. For drug delivery applications, there is a need to identify an optimal material that is cost-effective, compatible with ‘soft-lithography,’ easily replica molded, and resistant to harsh solvents. The family of thiol-ene polymers hold promise as an inexpensive and easy-to-produce alternative. This material shows good chemical compatibility with most organic solvents but falls short for chlorinated solvents which are often used for pharmaceutical applications. Thus, the research presented in this thesis aimed to develop a solvent compatible thiol-ene platform for rapid and cost-effective fabrication of microfluidic chips with a focus on drug delivery applications. This work initially shows the rendering of thiol-ene polymers chloroform compatible in order to open new prototyping avenues for drug delivery purposes. The approach is simple and effective, resulting in a 50-fold increase in chloroform compatibility, allowing for the operation of microfluidic chips in chloroform for several days without any discernible deformation. Next, this thesis shows the novel preparation of small (1-2 μm), monodispersed polylactic acid (PLA) microspheres, utilizing chlorinated solvents for their synthesis. This work presents a simple microfluidic chip design achievable in all microfluidic fabrication labs and relies on flow manipulations to shear of droplets well under the often-regarded minimum size limits. The prepared particles show high monodispersity and significant loading with magnetite nanoparticles; hence, hold promise for magnetically targeted drug delivery. In addition to droplet production, thiol-enes are suited for the bulk precipitation of uniform nanoparticles. The final work presented here focuses on siRNA loading within the lipid-polymer hybrid nanoparticles. This work shows exquisite size control, ranging from 70-300 nm, uniform sizes, and high siRNA encapsulation efficiency. The results obtained during this study presents a facile method to produce cost-effective and solvent compatible thiol-ene microfluidic chips highly suitable for numerous applications. With extensive experimental evidence, the fabricated thiol-ene microfluidic chips are shown to be very efficient for the production of pharmaceutical delivery vehicles of all sizes, ranging from the nano- to the micro-scale.

Text

2020-10-28

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/76387

Pharmaceutical Sciences

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/