Dowd-ICES Fellowship
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Gordon Christopher
Mechanical Engineering Project Title: Microfluidic Synthesis of Structured Particles for Drug Delivery Gordon Christopher's Research Presentation (Powerpoint File) |
Conventional approaches to synthesizing polymeric particles for controlled release of drugs involve
bulk emulsification in the presence of vigorous mixing. One problem with these methods is that the
result is frequently a heterogeneous population of particles with widely varying size and microstructure.
Size is particularly important since it is a key factor in the rate of release, and also it is known that
cells process particles used for non-viral gene delivery differently depending on their size. In contrast,
Microfluidic methods have previously been demonstrated as an effective platform for generating highly
monodisperse emulsions. Using microfluidic channels, two immiscible liquids will flow into a t-junction
and dropletw will be sheared off one liquid phase by the viscous stresses induced by the other liquid.
By forming droplets from a polymeric material combined with appropriate initiators we have the ability
to subsequently apply external stimuli like heat and light to trigger gelation or polymerization.
The initial stage of this research program probes two main issues. One part of the project involves
optimizing the initial drop formation. Droplet size is influenced by such factors as liquid flow rates,
device geometry, viscosities, and interfacial tension. Though the general dependence of drop size on each
of these parameters is known, comprehensive experiments over the full range of parameter space and
development of an accompanying predictive model is lacking. More importantly, polymers and surface
active molecules that are typically used in drug delivery dramatically influence the bulk and interfacial
properties, and their effects on drop formation are not well understood. Using a high speed CCD camera,
we will characterize droplet size as a function of those parameters listed. The outcome of this part
of the project will be a model that characterizes the relationship between the microfluidic parameters
and the droplet sizes.
The second part of the project will proceed concurrently with the drop formation study. Controlling the
local chemical and thermal environment of a droplet is key to directing its transformation into a gel or
polymer particle. Our goal is first to mimic conventional processes in a microfluidic device (thermal
gelation, emulsion or interfacial polymerization) using inline heating elements, focused UV light, and
additional fluid lines to introduce chemical initiators. We expect that microfluidic devices will offer
access to regions of parameter space that are not convenient in traditional methods. The outcome of this
part will be a model characterizing physical and mechanical properties of particles as a function of
processing conditions. This knowledge is vital to drug delivery since these properties influence the
ability of a particle to adhere to a targeted surface and to release its contents in a desired manner.
Further, geometric confinement during gelation and sequential application of microfluidic elements allows
us to think beyond uniform spherical shapes and consider novel shapes (plugs, rods) and microstructures
(core-shell, dual-sided, multiple emulsions).