Immersive Polymer Assembly on Immobilized Particles for Automated Capsule Preparation

摘要

We report a versatile approach for polymer capsule preparation using immobilized particles, which are immersed into polymer solutions either manually or by using an automated robotic dipping machine. This technique produces polyelectrolyte capsules with improved retention over conventionally prepared capsules. Additionally, responsive hydrogel capsules of different diameter can be prepared simultaneously. Polymer capsules are of significant interest for a range of biomedical applications because they can be prepared with tailored physicochemical properties, and can be engineered to encapsulate and release therapeutics and target specific cells. Layer-by-layer (LbL)-engineered particles and capsules1 represent a particular class of materials that have received widespread interest,2 as they can be prepared with different sizes,2-4 shapes,4 and mechanical strengths.5 These particles and capsules have also been examined for application in drug and vaccine delivery because they can be engineered to exhibit stealth,6 targeting,7 and stimuli-responsive properties.8 Despite the progress made in this field of research, the sequential layering process used to assemble the polymer multilayers on the precursor particles is often labor intensive and time consuming. A number of studies have focused on streamlining LbL assembly on templates by utilizing filters or microfluidic devices.9 However, these systems remain limited, as they do not offer the broad versatility inherent to conventional LbL assembly with regard to the choice of template particle size and exploitation of different polymer interactions. Further, issues arise from filter composition, pore size, channel width and recovery method, which lead to engineering challenges such as membrane caking, channel clogging, or a low-throughput of capsules. Recently, we reported the concept of immobilizing template particles in agarose gels for the rapid and versatile layering of particles using electrophoretic polymer assembly (EPA).10 Although EPA is useful for preparing a range of LbL-assembled capsules with useful material properties, uncharged polymers remain difficult to electrophorese, thus limiting the full range of materials and functionalities inherent to conventional LbL assembly. Herein, we report an approach to prepare polymer capsules based on layering on immobilized particle templates that retains the inherent benefits of conventional LbL assembly, is applicable to uncharged polymers, allows parallel layering of different particles and/or polymers, and is easily automatable. Immobilizing sacrificial particles in a gel essentially permits the complexity of layering on three-dimensional substrates to be treated as a two-dimensional, planar scenario. Therefore, immersive polymer assembly (IPA) on immobilized particles can use standard, planar dip-layering protocols11 with little modification. Similar to LbL assembly on planar substrates, immersing the immobilized particles in polymer solution results in polymer assembly on the particle surface. After recovering the layered particles from agarose and subsequently removing the template particles, stable capsules of different diameters are obtained (Scheme 1). Furthermore, IPA can be used with a StratoSequence robotic dipper (Nanostrata Inc.) for automated LbL assembly.[11] The biologically derived polysaccharide, agarose, was used as an immobilizing gel because the pore size is highly heterogeneous, on the order of 100 nm, and because polymers are capable of diffusing through the large agarose fibers, which are roughly 50–100 nm in diameter.12 However, rhodamine isothiocyanate (RITC) labeling of the agarose shows that there is also a larger pore size population with a range of 1–10 μm (Figure S1, Supporting Information). These pores have historically been conducive to the separation of biomolecules utilizing an electric current, but they also allow for polymers and other materials to passively diffuse through the gel without signi