Kaveh Yazdani Motlagh

Topic

Microfluidic Fabrication of Enteric-Coated Liquid-Core ATPS Capsules for Colon-Targeted Probiotic Delivery

Department of Mechanical Engineering

Date & location

• Wednesday, April 22, 2026

• 9:00 A.M.

• Virtual Defence

Reviewers

Supervisory Committee

• Dr. Mina Hoorfar, Department of Mechanical Engineering, University of Victoria (Supervisor)

• Dr. Mohsen Akbari, Department of Mechanical Engineering, UVic (Member)

• Dr. Stephanie Willerth, School of Medical Sciences, UVic (Outside Member) 

External Examiner

• Dr. Ali Dolatabadi, Department of Mechanical & Industrial Engineering, University of Toronto 

Chair of Oral Examination

• Dr. Ardeshir Shojaeinasab, Department of Electrical and Computer Engineering, UVic

   

Abstract

Colon-targeted delivery of live probiotics remains challenging because gastric acidity and intestinal bile salts can severely reduce viability, while premature leakage can prevent sufficient dosing at the site of action. This dissertation presents a simplified microfluidic platform for producing enteric-coated, liquid-core, hydrogel-shell capsules for colon delivery. The system generates water-in-water-in-oil (W/W/O) double emulsions using a poly(ethylene glycol) (PEG) and dextran aqueous two-phase system (ATPS) in a flow-focusing device, with improved droplet stability enabled by increasing channel height at the oil junction and avoiding complex surface treatments. 

The capsule architecture integrates (i) a PEG-based liquid core for high cargo loading, (ii) a dextran/alginate/Ca–ethylenediaminetetraacetic acid (EDTA) shell that is crosslinked on-chip via acid-triggered Ca²⁺ release, and (iii) a layer-by-layer coating of chitosan and Eudragit S100 nanoparticles to provide upper-GI protection and pH-responsive gating. To generate Eudragit S100 nanoparticles, a dedicated microfluidic micromixer was designed for continuous antisolvent nanoprecipitation (acetone→water), enabling rapid, reproducible mixing and supporting uniform enteric coating of the capsules. To explain and control emulsion morphology, volume-of-fluid computational fluid dynamics (CFD) simulations were coupled with targeted experiments to quantify necking dynamics and internal recirculation patterns, clarifying how shell viscosity and geometric confinement promote either one-core or two-core morphologies. 

Capsule performance was evaluated under sequential exposure to simulated gastric fluid (SGF, 0 2 h) and simulated intestinal fluid (SIF, 2–6 h). Uncoated capsules showed poor gastric protection, with Escherichia coli Nissle 1917 (EcN) viability decreasing to 62% after 1 h and reaching 0% by 2 h in SGF. In contrast, chitosan-coated capsules maintained high SGF viability (93% at 1 h; 89% at 2 h), while the Eudragit+chitosan multilayer achieved the highest survival (97% at 1 h; 95.2% at 2 h). After transfer to SIF, both coated formulations remained highly protective, with the Eudragit+chitosan capsules sustaining a consistent ~5.9–6.1 percentage-point advantage over chitosan alone from 2–6 h (95.2→93.0% vs 89→87.1%). Functional assays demonstrated strong retention during simulated upper-GI transit, with negligible release in SGF (0–2 h) and low cumulative release (6.7%) after sequential SGF→SIF exposure (0–6 h). Under colon-mimicking conditions with simulated colonic fluid (SCF) containing dextranase, release followed a lagacceleration–plateau behavior, reaching ~85–90% by ~3–6 h and ~95–100% by ~7–8 h, consistent with enteric dissolution and enzyme-driven shell loosening. 

Keywords: Colon-target delivery, Microfluidics, ATPS, Double emulsion, Probiotics, Enteric coating, Hydrogel capsules, W/W/O double emulsions.