Microfluidic Emulsion Templating, Directional Solidification and Controlled Release

Lead Research Organisation: Imperial College London
Department Name: Department of Chemical Engineering

Abstract

Microcapsules and particles offer efficient means of carrying and delivering active ingredients, including medical drugs and cosmetics, with precise spatio-temporal release profiles. Mechanistic understanding of the encapsulation, solidification and release processes is crucial in designing future microcapsules, combining thermodynamics, mass transfer and non-equilibrium phenomena, including kinetic arrest or phase changes. Emulsion droplets, generated within microfluidic devices, which can form a barrier between the cargo and external environment can be used to template microcapsules from, by directional solidification processes, and are being investigated to tackle this challenge.
Rapidly prototyped microfluidic devices, produced by frontal photopolymerization of thiol-ene resists, with flow-focussing geometries, and 200-600 micrometers dimensions, were used to generate single and double emulsion droplets from several polymeric, amphiphilic and hydrophobic species. Directional solidification processes, e.g. solvent extraction and ionic crosslinking, were exploited to form solid capsules from the droplets. The effects of varying process parameters, such as multivalent salt concentration or non-solvent quality, as well as the materials used on the solidification process and particle/capsule morphology was observed primarily by optical microscopy. Hydrogel particles (100-500 micrometers) were formed from single emulsion droplets of sodium carboxy methylcellulose (NaCMC) and solidified in multivalent salts. Gel particle formation was thought to be a result of aggregation of polymer chains; dictated by the interplay of shielding, ion bridging and charge inversion occurring upon salt addition. Solid polymer particles were also produced by a solvent extraction process; immersion of aqueous poly (vinyl alcohol) droplets, from a microfluidic single emulsion generator, into a non-solvent bath. Polymer concentration and non-solvent quality affected the morphology of the resultant particles and the kinetics of the directional solidification process. This versatility of this approach was shown by also solidifying aqueous NaCMC droplets into solid particles.
Further understanding of these directional solidification processes, their response to changes in molecular structure, processing parameters and flow, will enable them to be applied to encapsulation. Double emulsion droplets with an inner core of hydrophobic material, can be solidified by these methods to produce solid shells. Their potential application in a wide range of industries, from pharmaceuticals to personal care, will be demonstrated by studying their controlled release properties.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/P51052X/1 01/10/2016 30/03/2022
2292548 Studentship EP/P51052X/1 01/10/2016 31/03/2020 William Nicholas Sharratt
 
Description Polymeric materials are often processed by initially taking a fluid precursor (polymer solution or molten polymer), shaping the fluid and solidifying to arrest the shape. Here we use micro-scale manipulation of polymer solutions to create droplets and demonstrate that that can be solidified into particles and capsules with prescribed internal structures with two distinct methods; droplet solvent extraction and ionic gelation. The former utilises an additional solvent which extracts the droplet solvent, often water, to concentrate the polymer and create a solid skin. The latter uses a charged polymer which crosslinks and forms a solid gel upon addition of a multivalent salt. Such particles and capsules find application in drug delivery, personal care and agrichemicals. As a result of this award we have resolved the physico-chemical parameters underpinning the particle/capsule formation in both cases including using small-angle neutron scattering to address the problem at the nano-scale. Armed with this knowledge our results can facilitate molecular design of the particle/capsule structure to impart desired encapsulation and release properties in their application.
Exploitation Route Others may use the published results to inform their particle/capsule design and test them for a given application.
Sectors Agriculture, Food and Drink,Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Title Conformation and Phase Behavior of Sodium Carboxymethyl Cellulose in the Presence of Mono- and Divalent Salts 
Description Data from Sharratt et al., Macromolecules,2020 (10.1021/acs.macromol.9b02228) Figures in which data is transformed or the values are given in tables/supplementary information are not included. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact Allows researchers in polyelectrolyte physics, with particular relevance for interaction of charged biopolymers with biologically relevant salts, to access data and directly model/compare with their data to uncover universal phenomena. 
URL https://zenodo.org/record/3668725#.YD0CZlX7Spo
 
Title Microfluidic solvent extraction of poly(vinyl alcohol) droplets: effect of polymer structure on particle and capsule formation 
Description Raw data from the majority of figures of our 2018 Soft Matter Paper: Selected datasets from figures are excluded, owing to them being transformations of the raw data provided in the same figure. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact Facilitating translation of data and conclusions surrounding particle formation to real-world application in particle design for encapsulation and release. 
URL https://zenodo.org/record/2627324
 
Description Industrial Partnership 
Organisation Procter & Gamble
Department Procter & Gamble (United Kingdom)
Country United Kingdom 
Sector Private 
PI Contribution We undertook research as per the project award and presented results to P&G in regular meetings.
Collaborator Contribution P&G provided in-kind supervision, including guidance based on their industry knowledge and interpretation of our results. They offered access to their internal network for technical experts and facility access (if required).
Impact Outcomes are as per the award outcomes given this was an iCASE studentship and P&G were the industrial partner.
Start Year 2016
 
Description Microfluidic Micro- and Nano- Particle Formation 
Organisation Princeton University
Country United States 
Sector Academic/University 
PI Contribution Following a visit from Professor Rod Priestley (Princeton University, Chemical and Biological Engineering) to Imperial College London, I had been successfully award a RSC mobility grant to visit his Lab and Princeton for a month in 2018 to run some experiments which we had discussed during his visit. Since then, we have prepared a draft manuscript and been awarded 2 days of central facility use at a European neutron facility (ILL) to perform more experiments.
Collaborator Contribution Professor Rod Priestley supported my mobility grant with an in-kind contribution for the visit including accommodation, equipment access in their laboratory and the universities new, material characterization suite as well as providing samples for future experiments.
Impact No formal outputs or outcomes from this developing collaboration.
Start Year 2018