Fabrication of Highly Ordered Polycaprolactone Microspheres for In Vitro Drug Delivery Using Microfluidic Technologies
Alejandro Forigua a, Rebecca Kirsch b, Laila Abelseth c, Stephanie Willerth b c d, Katherine Elvira a
a Department of Chemistry, University of Victoria, Canada.
b Department of Mechanical Engineering, University of Victoria, Canada.
c Centre for Biomedical Research, University of Victoria, Canada
d Division of Medical Sciences, University of Victoria, Canada.
Proceedings of Emerging Investigators in Microfluidics Conference (EIMC)
Online, Spain, 2021 July 20th - 21st
Organizers: Adrian Nightingale, Darius Rackus and Claire Stanley
Oral, Alejandro Forigua, presentation 033
DOI: https://doi.org/10.29363/nanoge.eimc.2021.033
Publication date: 5th July 2021

The miniaturization of manufacturing processes using microfluidics (MF) has been increasingly used in chemistry, biology and engineering, due to advantages in terms of cost, size and control. The fabrication of small, uniformly-sized polymer microspheres (MS) using MF has been done to a small extent using materials such as glass capillaries, polytetrafluoroethylene (PTFE), and once using polydimethylsiloxane (PDMS). Here we show a new MF platform for the manufacture of polycaprolactone (PCL) MS for drug delivery using PDMS. This platform uses a flow-focusing geometry for droplet formation and takes advantage of a highly viscous PCL solution in dichloromethane (DCM), as the inner phase (IP), and a 2% polyvinyl alcohol (PVA) solution in water, as the outer phase (OP), to achieve a jetting regime. This forms MS of sizes around 30 micrometers, which are 8 times smaller than prior MF methods using PDMS, and twice as small as methods using other materials. Due to the hydrophobicity of PDMS, surface chemistry modification was necessary to make the channels in the device hydrophilic. High-speed imaging and Scanning Electron Microscopy (SEM) were used for the measurement of MS size. A 50% increase in the flow rate of the OP reduced the size of the MS by 30%; and a 5-fold increase of the OP flow rate compared to the IP flow rare reduces the MS size by 57%. Our new microfluidic design increases the throughput of uniformly-sized MS and reduces by a factor of 4 the starting materials and the fabrication time, when compared to batch production methods. We also include data to show how these MS interact with artificial cell membranes, using a platform of droplet interface bilayers (DIBs). These DIBs are lipid bilayers formed by with droplets containing a buffer system similar to real cells. This platform allows us to model a biological system, studying transport and quantification of drug delivery across artificial membranes, as well that allow us to have a new platform for the development of new materials for drug releasing particles.

Dr. Willerth receives funding from the NSERC Discovery Grant program, the Canada Research Chairs program, the Michael Smith Foundation for Health Research and the Pacific Parkinson’s Research Institute. Dr. Elvira receives funding from the Canada Research Chairs program, and the Michael Smith Foundation for Health Research Scholar program in partnership with the Pacific Alzheimer Research Foundation. Alejandro Forigua is funded through Dr. Elvira’s NSERC Discovery Grant.

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