Customizing polyelectrolyte complex shapes through photolithographic directed assembly.

Polyelectrolyte complexes (PECs) form through the association of oppositely charged polymers and, due to their attractive properties, such as their mild/simple preparation and stimulus-sensitivity, attract widespread interest. The diverse applications of these materials often require control over PEC shapes. As a versatile approach to achieving such control, we report a new photolithographic directed assembly method for tailoring their structure. This method uses aqueous solutions of a polyelectrolyte, an oppositely charged monomer and a photoinitiator. Irradiation of these mixtures leads to site-specific polymerization of the ionic monomer into a polymer and, through this localized polyanion/polycation mixture formation, results in the assembly of PECs with 2-D and 3-D shapes that reflect the photoirradiation pattern. In addition to generating macroscopic PECs using photomasks, this photodirected PEC assembly method can be combined with multiphoton lithography, which enables the preparation of custom-shaped PECs with microscopic dimensions. Like other PECs, the custom-shaped structures formed through this photodirected assembly approach are stimulus-responsive, and can be made to switch shape or dissolve in response to changes in their external environments. This control over PEC shape and stimulus-sensitivity suggests the photopolymerization-based directed PEC assembly method as a potentially attractive route to stimulus-responsive soft device fabrication (e.g., preparation of intricately shaped, function-specific PECs through photolithographic 3-D printing).

Photolithographically assembled polyelectrolyte complexes as shape-directing templates for thermoreversible gels.

Preparation of soft materials with diverse, customized shapes has been a topic of intense research interest. To this end, we have recently demonstrated photolithographic directed assembly as a strategy for customizing polyelectrolyte complex (PEC) shape. This process uses in situ photopolymerization of an anionic monomer in the presence of a cationic polymer, which drives localized PEC formation at the irradiation sites. Here, we show how such photolithographically assembled PECs can serve as structure-directing templates for tailoring the shapes of other soft materials; namely, thermoreversible gels. These templated hydrogels are prepared by adding a thermogelling polymer (agarose) to the anionic monomer/cationic polymer/photoinitiator precursor solutions so that, upon irradiation, custom-shaped PECs form within agarose gel matrices. Once these PECs are formed, the surrounding agarose gels are melted (through heating) and washed away which, upon returning the samples to room temperature, produces interpenetrating PEC/agarose gel networks with photopatterned shapes and dimensions. Dissolution of these sacrificial PEC templates in concentrated NaCl solutions then generates photolithographically templated agarose gels, whose shapes and dimensions match those of their PEC templates. Besides tuning their shapes and sizes, the mechanical properties of these gels can be easily tailored by varying the initial agarose concentrations used. Moreover, this PEC-templated gel synthesis appears to not adversely affect hydrogel cytocompatibility, suggesting its potential suitability for biological and biomedical applications. Though the present study uses only agarose as the model gel system, this PEC-based strategy for customizing gel shape can likely also be applied to other thermoreversible gel networks (e.g., those based on methylcellulose, poloxamers or thermoresponsive chitosan derivatives) and could have many attractive applications, ranging from drug delivery and tissue engineering, to sensing and soft robotics.

Poly(allylamine)/tripolyphosphate coacervates enable high loading and multiple-month release of weakly amphiphilic anionic drugs: an in vitro study with ibuprofen.

When synthetic polyamines, such poly(allylamine hydrochloride) (PAH), are mixed with crosslink-forming multivalent anions, they can undergo complex coacervation. This phenomenon has recently been exploited in various applications, ranging from inorganic material synthesis, to underwater adhesion, to multiple-month release of small, water-soluble molecules. Here, using ibuprofen as a model drug molecule, we show that these coacervates may be especially effective in the long-term release of weakly amphiphilic anionic drugs. Colloidal amphiphile/polyelectrolyte complex dispersions are first prepared by mixing the amphiphilic drug (ibuprofen) with PAH. Pentavalent tripolyphosphate (TPP) ions are then added to these dispersions to form ibuprofen-loaded PAH/TPP coacervates (where the strongly-binding TPP displaces the weaker-bound ibuprofen from the PAH amine groups). The initial ibuprofen/PAH binding leads to extremely high drug loading capacities (LC-values), where the ibuprofen comprises up to roughly 30% of the coacervate mass. Conversely, the dense ionic crosslinking of PAH by TPP results in very slow release rates, where the release of ibuprofen (a small, water-soluble drug) is extended over timescales that exceed 6 months. When ibuprofen is replaced with strong anionic amphiphiles, however (i.e., sodium dodecyl sulfate and sodium dodecylbenzenesulfonate), the stronger amphiphile/polyelectrolyte binding disrupts PAH/TPP association and sharply increases the coacervate solute permeability. These findings suggest that: (1) as sustained release vehicles, PAH/TPP coacervates might be very attractive for the encapsulation and multiple-month release of weakly amphiphilic anionic payloads; and (2) strong amphiphile incorporation could be useful for tailoring PAH/TPP coacervate properties.

Preparation and Timed Release Properties of Self-Rupturing Gels.

Swelling of polymeric hydrogels is sensitive to their cross-link densities. Here, we exploit this principle to prepare self-rupturing gels which are based on a commonly-used, nontoxic, and inexpensive polyelectrolyte, poly(acrylic acid), and are prepared through a simple and low-cost polymerization-based technique. The self-rupture of these covalently cross-linked gels is achieved by preparing them to have highly nonuniform cross-link densities. This heterogeneity in cross-linking leads to highly nonuniform swelling, which generates stresses that are high enough to induce gel rupture. The time required for this rupture to occur depends on the difference in the cross-link densities between the adjoining gel regions, gel size, order in which the variably cross-linked gel portions are synthesized, and on the ambient pH and ionic strength. Furthermore, when these self-rupturing gels are prepared to have liquid-filled (capsule-like) morphologies, they can act as timed/delayed release devices. The self-rupture of these capsules provides a burst payload release after a preprogrammed delay, which is on the timescale of days and can be easily tuned by varying the rupture time, i.e., by varying either the cross-link nonuniformity or the pH and ionic strength of the release media.

Simple preparation of polyelectrolyte complex beads for the long-term release of small molecules.

We report a simple method for preparing solid polyelectrolyte complex (PEC) beads, which provide effective barriers to diffusion and can be used for the multiple-day release of small molecules. Single-phase poly(allylamine) (PAH) and poly(styrenesulfonate) (PSS) mixtures were prepared at pH 11.6 (significantly above the effective pKa of PAH), where the PAH amine groups were deprotonated and therefore neutral. These mixtures were added dropwise into acid baths, whereupon the rapid acid diffusion into the polyelectrolyte droplets led to instant ionization of PAH amine groups and, thus, the formation of PEC beads (i.e., via phase inversion). In stark contrast to the PEC particles prepared through phase inversion in previous studies, which had (solvent-filled) capsule-like morphologies, these beads had solid internal structures. The solute permeabilities of these PEC matrices could be extensively tuned by air drying the beads, which led to the apparently-irreversible closure of pores. Thus, by tuning the drying conditions and polymer compositions used during bead preparation, a model small molecule (Fast Green FCF dye) was released over times ranging between 2 and 18 days.