Tuning the Properties of Layer-by-Layer Assembled Poly(acrylic acid) Click Films and Capsules

The combination of click chemistry and layer-by-layer (LbL) assembly provides a useful and convenient means of preparing functional, covalently stabilized films and capsules. Herein, we examine various parameters that affect the buildup of click-LbL assembled multilayers of azide- and alkyne-modified poly(acrylic acid) (PAAAz and PAAAlk, respectively). We demonstrate that film thickness and morphology can be tailored by varying the assembly conditions. The thicknesses of multilayers assembled from PAAAz and PAAAlk [(PAAAz/PAAAlk)5] on planar substrates varied from ∼70 nm when assembled at pH 2.5 to 10 nm when prepared at pH 4. Increasing the ionic strength of the adsorption solution resulted in an increase in the (PAAAz/PAAAlk)5 film thickness, with a maximum of ∼30 nm observed for solutions with ionic strengths of 150 mM and greater. A deposition time of 5 min was found to give close to saturated adsorbed layer amounts. Additionally, the influence of the click moieties on multilayer assembly was investigated. By altering the azide content of PAAAz and maintaining the alkyne content of PAAAlk at ∼15%, the thicknesses of (PAAAz/PAAAlk)5 films were shown to increase exponentially from about 20 nm at 5% azide functionalization of PAAAz to 90 nm at 30% azide functionalization of PAAAz. Furthermore, atomic force microscopy measurements showed distinct morphological changes (i.e., enhanced porosity and/or creases and folds) for (PAAAz/PAAAlk)5 films prepared from PAAAz with different azide contents at pH 3.5 when subjected to basic conditions (pH 10). This was attributed to the different cross-linking degree between the multilayers. The current study was extended to the assembly of hollow polymer capsules to determine an optimum range of 10−20% azide functionalization of PAAAz for the assembly of click polymer capsules

Modular Assembly of Layer-by-Layer Capsules with Tailored Degradation Profiles

Herein we report the preparation of layer-by-layer (LbL) assembled, biodegradable, covalently stabilized capsules with tunable degradation properties. Poly(l-glutamic acid) modified with alkyne moieties (PGAAlk) was alternately assembled with poly(N-vinyl pyrrolidone) (PVPON) on silica particles via hydrogen-bonding. The films were cross-linked with a bis-azide linker, followed by removal of the sacrificial template and PVPON at physiological pH through hydrogen bond disruption, yielding one-component PGAAlk capsules. To control the kinetics and location of capsule degradation, a number of approaches were investigated. First, a degradable bis-azide cross-linker was incorporated into the inherently enzymatically degradable capsules. Second, we assembled low-fouling capsules composed of nondegradable poly(N-vinyl pyrrolidone-ran-propargyl acrylate) (PVPONAlk) via hydrogen bonding with poly(methacrylic acid) (PMA) and combined this with the aforementioned system (PGAAlk/PVPON) to produce stratified hybrid capsules. The degradation profiles of these stratified capsules can be closely controlled by the number as well as the position of nondegradable barrier layers in the systems. The facile tailoring of the degradation kinetics makes this stratified LbL approach promising for the design of tailored drug-delivery vehicles

Control of Photochromism through Local Environment Effects Using Living Radical Polymerization (ATRP)

Control of Photochromism through Local Environment Effects Using Living Radical Polymerization (ATRP

Rapid Photochromic Switching in a Rigid Polymer Matrix Using Living Radical Polymerization

Fast switching of a photochromic dye in a rigid host matrix has been achieved without any modification of electronic nature of the photochromic entity. The method utilizes living radical polymerization (atom transfer radical polymerization (ATRP)) to grow a low glass transition temperature (Tg) poly(n-butyl acrylate) polymer from a spirooxazine core, creating a low-Tg environment to cushion the photochromic dye while keeping the bulk matrix rigid. In these systems, decoloration speed of the photochromic (t1/2) was reduced by 40−75% depending on the molecular weight of the poly(n-butyl acrylate) attached. We have demonstrated with this methodology a controlled tuning of photochromic switching. Coarse and fine tuning can be achieved by adjusting first the choice of polymer and second the molecular weight of the polymer

Low-Fouling, Biofunctionalized, and Biodegradable Click Capsules

We report the synthesis of covalently stabilized hollow capsules from biodegradable materials using a combination of click chemistry and layer-by-layer (LbL) assembly. The biodegradable polymers poly(l-lysine) (PLL) and poly(l-glutamic acid) (PGA) were modified with alkyne and azide moieties. Linear film buildup was observed for both materials on planar surfaces and colloidal silica templates. A variation of the assembly conditions, such as an increase in the salt concentration and variations in pH, was shown to increase the individual layer thickness by almost 200%. The biodegradable click capsules were analyzed with optical microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). Capsules were uniform in size and had a regular, spherical shape. They were found to be stable between pH 2 and 11 and showed reversible, pH-responsive shrinking/swelling behavior. We also show that covalently stabilized PLL films can be postfunctionalized by depositing a monolayer of heterobifunctional poly(ethylene glycol) (PEG), which provides low-fouling properties and simultaneously enhances specific protein binding. The responsive, biodegradable click films reported herein are promising for a range of applications in the biomedical field

Polyglyoxylamides with a pH-Mediated Solubility and Depolymerization Switch

Self-immolative polymers (SIPs) are characterized by their ability to depolymerize in response to the cleavage of a single end-cap or backbone moiety, making them attractive for numerous applications including sensors, transient plastics, and delivery vehicles. For many applications, it would be desirable to have an SIP capable of depolymerizing selectively under mildly acidic aqueous conditions. However, the poor solubility of most SIPs in water, accompanied by the competing effects of end-cap cleavage and depolymerization mechanisms, has made this a challenge. Here, we describe the development of polyglyoxylamides (PGAms) with pendent amino groups to achieve solubility switching at mildly acidic pH, which allows access of water to the end-cap and consequently depolymerization. PGAms with varying amino groups were synthesized from trityl end-capped poly­(ethyl glyoxylate) (PEtG). While water-insoluble PEtG underwent no detectable depolymerization between pH 5 and 7.4 and water-soluble PGAms underwent rapid depolymerization regardless of pH in this range, a PGAm with N,N-diisopropylaminoethyl (DPAE) pendent groups underwent more rapid depolymerization at pH 5–6 compared to pH 7.4. PGAms were also incorporated into block copolymers with poly­(ethylene glycol) (PEG). Nanoassemblies formed from PEG-PGAm­(DPAE), swelled, disassembled, and depolymerized as the pH was lowered from 8 to 5. Copolymers lacking a solubility switch did not undergo pH-dependent disassembly or depolymerization. Overall, this work provides a new platform approach for the development of pH-sensitive SIP materials for a wide range of applications

Acid-Responsive Poly(glyoxylate) Self-Immolative Star Polymers

Self-immolative polymers have significant potential for applications such as drug or gene delivery. However, to realize this potential, such materials need to be customized to respond to specific variations in biological conditions. In this work, we investigated the design of new star-shaped self-immolative poly­(ethyl glyoxylate)­s (PEtGs) and their incorporation into responsive nanoparticles. PEtGs are a subclass of stimulus-responsive self-immolative polymers, which can be combined with different stimuli-responsive functionalities. Two different tetrathiol initiators were used for the polymerization in combination with a variety of potential pH-responsive end-caps, yielding a library of star PEtG polymers which were responsive to pH. Characterization of the depolymerization behavior of the polymers showed that the depolymerization rate was controlled by the end caps rather than the architecture of the polymer. A selection of the star polymers were modified with amines to allow introduction of charge-shifting properties. It was shown that pH-responsive nanoparticles could be prepared from these modified polymers and they demonstrated pH-dependent particle disruption. The pH responsiveness of these particles was studied by dynamic light scattering and 1H nuclear magnetic resonance spectroscopy

Ultrathin, Responsive Polymer Click Capsules

We report a general click chemistry approach for the layer-by-layer assembly of ultrathin, polymer films on particles and the subsequent formation of polymer click capsules (CCs). Poly(acrylic acid) copolymers, synthesized with a minor component of either alkyne (PAA-Alk) or azide (PAA-Az) functionality, were alternately assembled on silica particles. The (PAA-Az/PAA-Alk)-coated particles were subsequently functionalized by exploiting the free alkyne click moieties present in the film upon exposure to an azide-modified rhodamine dye. Further, PAA CCs, obtained following removal of the silica particle template, were shown to exhibit pH-responsive behavior. This was demonstrated by reversible size changes of the CCs upon cycling between basic and acidic solutions. Polymer CCs are anticipated to find applications in various fields, including drug delivery and sensing

Assembly of Ultrathin Polymer Multilayer Films by Click Chemistry

Layer-by-layer (LbL) assembly is a versatile and robust technique for fabricating tailored thin films of diverse composition. Herein we report a new method of covalent coupling, click chemistry, to facilitate the LbL assembly of thin films. Linear film growth was observed using both UV−vis and FTIR spectroscopy, and film thicknesses were determined by ellipsometry and atomic force microscopy. The assembled films are shown to be stable in a wide pH range. This technique offers the potential to enable the synthesis of new types of stable and responsive LbL films from a variety of polymers

Biodegradable Click Capsules with Engineered Drug-Loaded Multilayers

We report the modular assembly of a polymer−drug conjugate into covalently stabilized, responsive, biodegradable, and drug-loaded capsules with control over drug dose and position in the multilayer film. The cancer therapeutic, doxorubicin hydrochloride (DOX), was conjugated to alkyne-functionalized poly(l-glutamic acid) (PGA_Alk) <i>via</i> amide bond formation. PGA_Alk and PGA_Alk+DOX were assembled <i>via</i> hydrogen bonding with poly(<i>N</i>-vinyl pyrrolidone) (PVPON) on planar and colloidal silica templates. The films were subsequently covalently stabilized using diazide cross-linkers, and PVPON was released from the multilayers by altering the solution pH to disrupt hydrogen bonding. After removal of the sacrificial template, single-component PGA_Alk capsules were obtained and analyzed by optical microscopy, transmission electron microscopy, and atomic force microscopy. The PGA_Alk capsules were stable in the pH range between 2 and 11 and exhibited reversible swelling/shrinking behavior. PGA_Alk+DOX was assembled to form drug-loaded polymer capsules with control over drug dose and position in the multilayer system (<i>e.g.</i>, DOX in every layer or exclusively in layer 3). The drug-loaded capsules could be degraded enzymatically, resulting in the sustained release of active DOX over ∼2 h. Cellular uptake studies demonstrate that the viability of cells incubated with DOX-loaded PGA_Alk capsules significantly decreased. The general applicability of this modular approach, in terms of incorporation of polymer−drug conjugates in other click multilayer systems, was also demonstrated. Biodegradable click capsules with drug-loaded multilayers are promising candidates as carrier systems for biomedical applications