Microfluidic Design of Multicompartmental Hydrogel Platforms for Programmable Encapsulation and Release

다국어 초록 (Multilingual Abstract)

Hydrogel based carriers have been widely investigated for encapsulation and controlled release because their hydrated polymer networks can accommodate various cargos under mild conditions. However, the intrinsic permeability of hydrogels often limits long term retention of small water soluble cargos and makes it difficult to independently control cargo protection and triggered release. This dissertation addresses this limitation by designing compartmentalized hydrogel capsules in which cargo reservoirs, barrier layers, and responsive hydrogel matrices are spatially organized to regulate molecular transport and release behavior. First, PNIPAm-co-PEGDA hydrogel microcapsules containing an interstitial thin oil layer were fabricated from W/O/W/O triple emulsion templates. The microcapsules consisted of an internal aqueous core, an intermediate oil barrier, and an outer thermos-responsive hydrogel shell. The thin oil layer retained small water soluble cargo at low temperature, while heating induced active release through oil barrier destabilization. The release temperature was not determined solely by the intrinsic thermal transition of PNIPAm, but was governed by the coupled effects of aqueous core expansion, hydrogel shell deswelling, shell mechanics, and oil barrier stability. By adjusting the crosslinking density and shell thickness, the release temperature was tuned over a broad range. In addition, gold nanorods incorporated into the shell enabled near infrared triggered local release through photothermal heating. Although this microscale platform demonstrated the barrier gate function of a thin oil layer, applications requiring larger cargo capacity, direct handling, structural observation, and multicargo organization require expansion of the same design principle to a larger capsule format. Therefore, the compartmentalized architecture was extended to millimeter scale multicore alginate macrocapsules for programmable oral delivery. In this system, multiple aqueous cores were separated by oil layers and collectively encapsulated within an alginate hydrogel shell using a one-step microfluidic fabrication strategy. The oil layers acted as internal barriers that reduced direct cargo exchange with the hydrogel matrix, while the alginate shell provided mechanical support and environment responsive release control. The platform enabled uniform macrocapsule production with high encapsulation efficiency and allowed control over capsule size, oil barrier volume, core organization, and cargo loading capacity. Under gastric like conditions, the multicore alginate macrocapsules showed mechanical robustness and protected encapsulated cargos from acidic and simulated gastric environments. Under simulated intestinal conditions, the alginate shell weakened through ion exchange driven network disruption, resulting in controlled cargo release. By changing the alginate concentration, release onset and cumulative release amount were programmed without altering the internal multicore architecture. The platform was further expanded to Janus and triple compartment structures, enabling sequential or simultaneous release of multiple cargos by assigning different or identical alginate shell formulations to each compartment. Overall, this dissertation demonstrates that compartmentalized hydrogel capsules can decouple cargo retention and triggered release through structural control of reservoirs, barriers, and responsive matrices. Importantly, the thin oil layer based barrier gate concept established in thermos-responsive microcapsules was extended to multicore alginate macrocapsules for oral delivery, showing that programmable release can be achieved by controlling capsule scale, geometry, barrier stability, matrix mechanics, and compartmental organization. This strategy provides a foundation for hydrogel based platforms for controlled release, oral delivery, and multicargo therapeutic applications.

목차 (Table of Contents)

• Chapter 1. Introduction and Background 1
• 1.1. Introduction 1
• 1.2. Hydrogel Networks as Permeable Matrices for Encapsulation 2
• 1.3. Compartmentalized Architectures for Regulating Molecular Transport 5
• 1.4. Droplet Microfluidics for Hydrogel Capsules 8
• 1.5. Stimuli Responsive Release through Coupled Barrier and Matrix Response 11
• 1.6. Objectives and Scope of This Dissertation 13
• Chapter 2. Mechanically Tunable Thermo-Responsive Hydrogel Microcapsules for Controlled Active Release 16
• 2.1. Introduction 16
• 2.2. Experimental Methods 20
• 2.2.1. Materials 20
• 2.2.2. Fabrication and Operation of the Glass Capillary Microfluidic Device 21
• 2.2.3. Fabrication of Thermo-responsive Hydrogel Microcapsules 22
• 2.2.4. Optical and Fluorescence Microscopy 23
• 2.2.5. Estimation of Microgel Compressive Modulus 24
• 2.3. Results and Discussion 25
• 2.3.1. Microfluidic Production of PNIPAm-co-PEGDA Hydrogel Microcapsules 25
• 2.3.2. Thermo-responsive Behavior and Active Release 33
• 2.3.3. Effect of Crosslinking Density on Release Temperature 40
• 2.3.4. Effect of Shell Thickness on Broad Range Temperature Control 52
• 2.3.5. NIR Triggered Local Release 47
• 2.4. Conclusion 64
• Chapter 3. Multicore Alginate Macrocapsules for Programmable Oral Delivery 66
• 3.1. Introduction 66
• 3.2. Materials and Methods 69
• 3.2.1. Materials 69
• 3.2.2. Preparation and Operation of Glass Capillary Microfluidic Devices 70
• 3.2.3. Fabrication of Multicore Alginate Macrocapsules 71
• 3.2.4. Characterization and Image Analysis 72
• 3.2.5 Preparation of Simulated Gastric Fluid and Simulated Intestinal Fluid 73
• 3.2.6 Mechanical Characterization 74
• 3.2.7 Analysis of Cargo Release Profiles 75
• 3.2.8 Fabrication of Multicompartmental Macrocapsules 76
• 3.3 Results and Discussion 77
• 3.3.1. One Step Microfluidic Fabrication of Multicore Alginate Macrocapsules 77
• 3.3.2. Control of Macrocapsule Dimensions and Multicore Organization 85
• 3.3.3. Structural Robustness and Cargo Protection under Gastric Conditions 91
• 3.3.4. Programmable Cargo Release in Simulated Intestinal Environments 101
• 3.3.5. Multicompartmental Macrocapsules for Programmable Multi Cargo Delivery 107
• 3.4. Conclusion 115
• Chapter 4. Overall Conclusion 117
• References 122
• Abstract 134
• Summary in Korean 137
• Curriculum Vitae 140