Sustained release control via photo-cross-linking of polyelectrolyte layer-by-layer hollow capsules

We describe the formation and permeability of polyelectrolyte multilayer hollow-shell capsules by photo-cross-linking and controlled-release (fluorescence) studies. The hollow shells were prepared by alternate layer-by-layer (LbL) adsorption of photo-cross-linkable benzophenone modified poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) on polystyrene particles, followed by removing the core with tetrahydrofuran. Zeta potential measurements, fourier transform infrared spectroscopy, and transmission electron microscopy were used to verify the LbL process integrity. A model drug, rhodamine B (RB), was successfully loaded into the polyelectrolyte hollow capsules. The release kinetics of RB was investigated using fluorescence spectroscopy. The permeability of RB through the hollow shells was effectively controlled based on UV irradiation time. It was shown that the release of RB molecules can be controlled by the degree of cross-linking induced in the multilayer.     

Loading and release behaviors of compressed polyelectrolyte multilayers for small dye molecules

Loading and release behaviors of compressed polyelectrolyte multilayers composed of poly(styrenesulfonate sodium salt) and poly(diallyldimethylammonium chloride) were investigated using fluorescein and rhodamine 6G as indicators by confocal laser scanning microcopy, fluorescence spectroscopy, and UV-vis spectroscopy. Compression of the multilayers resulted in a more densely packed microstructure, leading to the decrease of fluorescence intensity of the incorporated probes to 80% of its initial value, and much slower releasing rate as well as smaller releasing amount regardless of the types of the probes and the presence of salt. Utilizing the difference of loading and release rates between the compressed and the uncompressed regions, arrays of dye reservoirs have been fabricated on a chemical homogeneous but physical heterogeneous multilayer film.     

Water-soluble perylene diimides: Solution photophysics and layer-by-layer incorporation into polyelectrolyte films

Recently the synthesis of water-soluble and fluorescent perylene diimides has been reported (Müllen, K.; et al. Angew. Chem., Int. Ed. 2004, 43, 1528; Chem.-Eur. J. 2004, 10, 5297). We have characterized the photophysics of two of these compounds (anionic n-PDI, CAS Reg. No. 694438-88-5. and cationic p-PDI, CAS Reg. No. 817207-4-7) in pure water, dimethyl sulfoxide (DMSO), and aqueous NaCl. These studies, supported by molecular dynamics simulations, have led to the conclusion that these compounds form weakly interacting aggregated species in pure water. n-PDI and p-PDI have been incorporated in polyelectrolyte films of poly(styrene sulfonate) (PSS) and poly(diallyldimethylammonium chloride) (PDAC) following the layer-by-layer (LBL) methodology. The optical density and fluorescence intensity of the PDI-LBL films grew linearly with the number of layers, and the PDI was not extracted by subsequent polyelectrolyte deposition. The PDI fluorescence quantum yield was substantially diminished in these films, which we interpret as a self-quenching effect, enhanced by inter- and intralayer energy transfer. Energy-transfer studies to the incorporated cationic dye Brilliant Green (BG) has demonstrated that the BG resides in the same PSS-rich region as p-PDI and is largely excluded from the region that contains n-PDI (PDAC-rich).     

Phospholipid bilayers as biomembrane-like barriers in layer-by-layer polyelectrolyte films

Dipalmitoylphosphatidylcholine (DPPC) bilayer was created on the surface of an exponentially growing poly(glutamic acid)/poly(lysine) (PGA/PLL) layer-by-layer polyelectrolyte film. The lipid bilayer decreased the surface roughness of the polyelectrolyte film. The layer-by-layer construction of the polyelectrolyte film could be continued on the top of the DPPC layer. The lipid bilayer, however, formed a barrier in the interior of the polyelectrolyte film, which blocked the diffusion (a prerequisite for exponential growth) of the polyelectrolytes. Thus, a new growth regime started in the upper part of the polyelectrolyte film, which was added to embed the DPPC bilayer. The structure and the dynamics of the DPPC bilayer on the polyelectrolyte film surface remained similar to that of its hydrated multibilayers, except that the phase transition became wider. In the case of embedded DPPC bilayers, in addition, the phase-transition temperature also decreased. This is the result of interactions with the nonconcerted movements of the barrier-separated lower and higher parts of the polyelectrolyte film. Gramicidin A (GRA) as a model of lipid-soluble peptides and proteins was successfully incorporated into such DPPC films. The DPPC films, either with or without GRA, were remarkably stable; as many heating-cooling cycles to measure phase transition could be carried out without visible alterations as wanted.     

Spontaneous wrinkling of layer-by-layer assembled polyelectrolyte films for humidity-responsive superhydrophobicity

The fabrication of smart films with reversible wettability enabled by the stimulus-induced morphology changes has attracted growing interest but remains a challenge. Here we report a smart film that can reversibly changes its wettability between transparent hydrophobicity to translucent superhydrophobicity through the humidity-induced wrinkling/de-wrinkling process. The film was fabricated by depositing hydrophobic SiO₂ nanoparticles (NPs) on poly(acrylic acid) (PAA)/poly(allylamine hydrochloride) (PAH) films, followed by partially exfoliating the films from the underlying substrates. The partially exfoliated PAA/PAH film can reversibly wrinkle and de-wrinkle when being alternately subjected to humid and dry environments. The deposition of hydrophobic SiO₂ NPs on the wrinkling PAA/PAH film does not hinder the humidity-enabled wrin-kling/de-wrinkling ability of the composite film. The hydrophobic SiO₂ NPs and the underlying humidity-wrinkling PAA/PAH film enable the composite film to spontaneously change from hydrophobic and transparent to superhydrophobic and translucent with the rise of environmental humidity.     

Correlation of antithrombogenicity and heat treatment for layer-by-layer self-assembled polyelectrolyte films

Antithrombogenic films with high durability were fabricated in a wet process. Antithrombogenicity was achieved with polyelectrolyte multilayer thin film prepared from poly(vinyl alcohol)-poly(acrylic acid) (PVA-PAA) blends, deposited in alternate layers with poly(allylamine hydrochloride) (PAH). Film durability, assessed by abrasion resistance and water resistance, was enhanced by forming cross-links via amide bonds induced by heat treatment of the film. The film was found to be resistant to protein adsorption, as measured by the amount of fibrinogen adsorbed from an aqueous solution. The antithrombogenic efficacy was assessed in ex vivo experiments by the ability of stainless steel mesh, coated with the polyelectrolyte and inserted into a pig blood vessel, to inhibit thrombus formation. Mesh coated with the polyelectrolyte did not reduce blood flow over a period of 15 min, whereas with uncoated mesh blood flow stopped within 6 min because of blood vessel blockage by thrombus formation.     

Silver nanocomposite layer-by-layer films based on assembled polyelectrolyte/dendrimer

Silver nanocomposite multilayer films were prepared through the in situ method. Multilayer thin films, prepared through the sequential electrostatic deposition of a positively charged third-generation poly(amidoamine) dendrimer (PAMAM) and negatively charged poly(styrenesulfonate) (PSS) and poly(acrylic acid) (PAA), were utilized as nanoreactors for the formation of silver nanoparticles. The silver ions were preorganized in layer-by-layer (LBL) films composed of PAMAM dendrimers and subsequently reduced with hydrogen to prepare the silver nanoparticles. The UV-vis spectrum and profilometer were used to characterize the regular growth of bilayers. UV-vis absorption from plasmon resonance at 435 nm and TEM images indicated the formation of the silver nanoparticles in the multilayer films. The silver nanocomposite LBL films were also constructed on the indium tin oxide-glass and investigated using cyclic voltammetry. The silver nanoparticles in the multilayer films have a stronger negative redox potential. The silver nanocomposite LBL films may have a potential application in the catalysis of reduction of 4-nitrophenol with sodium borohydride.     

Encapsulation, release and applications of LbL polyelectrolyte multilayer capsules

Ever since their invention in 1998, polyelectrolyte multilayer micro- and nano-capsules have impacted various areas of biology, chemistry and physics. Here we highlight progress achieved since the millennium in the areas of encapsulation in and release from microcapsules, describe various structures including multicompartment and anisotropic constructs, and provide examples of several applications in biology. We also describe application areas such as drug delivery, intracellular trafficking, enzyme-catalyzed reactions, mechano-biology which benefited from recent developments in the area of polyelectrolyte multilayer capsules.     

Loading and release of small hydrophobic molecules in multilayer films based on amphiphilic polysaccharides

We report on the loading and release behaviors of polyelectrolyte multilayers based on hydrophobically modified carboxymethylpullulan (CMP) derivatives and poly(ethyleneimine) (PEI) toward hydrophobic dye. The dye-loaded films are obtained according to two different protocols: (i) the postdiffusion approach, which involves the diffusion of the dye within preassembled self-assemblies, and (ii) the precomplexation method, which requires the formation of a water-soluble amphiphilic CMP derivative-dye complex before the multilayer buildup. In both cases, we provide clear evidence for the entrapment of the dye in hydrophobic nanoreservoirs resulting from the aggregation of decyl pendent groups grafted on CMP chains. We show that the loading capacity of the multilayers, as well as their release behavior, can be tuned by varying the grafting degree of CMP chains. Moreover, we demonstrate the possibility to trigger the subsequent release of the loaded dye molecules by varying the composition of the surrounding solution.     

Polarity of layer-by-layer deposited polyelectrolyte films as determined by pyrene fluorescence.

The polarity of polyelectrolyte (PE) multilayer films is investigated with pyrene as a polarity-sensitive probe. Multilayer films of poly(styrene sulfonate) (PSS) and various polycations were prepared by the layer-by-layer self-assembly technique. Pyrene (PY) molecules were inserted into the films by exposing the multilayers to pyrene solutions. By this method a homogeneous distribution of pyrene molecules at low concentration within the film was obtained. The ratio of the fluorescence intensities of the first (I) to the third (III) vibronic band (Py-value) of the pyrene emission spectrum is employed here to determine the polarity of the PE films. PSS and poly(allylamine hydrochloride) (PAH) multilayer films yielded a pyrene value close to the solvent polarity of acetone, while multilayers of PSS and poly(diallyldimethylammonium chloride) (PDADMAC) displayed a value higher than the one corresponding to water. The pyrene values of the polyelectrolyte films were independent from the solvent employed for probe dissolving. Although no direct relationship between solvent polarity and dielectric constant (epsilon) is available, an estimate of the static dielectric constant of the films can be provided by comparing the Py-values of the films with those of various solvents. Changes in the humidity conditions of the film environment in a closed cell did not affect the film polarity. However, a drastic and irreversible reduction of polarity could be induced by actively drying the samples by a nitrogen flow.     

Balance of hydrophobic and electrostatic forces in the pH response of weak polyelectrolyte capsules

A detailed study of the role of solution pH and ionic strength on the swelling behavior of capsules composed of the weak polyelectrolytes poly(4-vinylpyridine) (P4VP) and poly(methacrylic acid) (PMA) with different numbers of layers was carried out. The polyelectrolyte layers were assembled onto silicon oxide particles and multilayer formation was followed by zeta-potential measurements. Hollow capsules were investigated by scanning electron microscopy and atomic force microscopy. The pH-dependent behavior of P4VP/PMA capsules was probed in aqueous media using confocal laser scanning microscopy. All systems exhibited a pronounced swelling at the edges of stability, at pHs of 2 and 8.1. The swelling degree increased when more polymer material was adsorbed. The swollen state can be attributed to uncompensated positive and negative charges within the multilayers, and it is stabilized by counteracting hydrophobic interactions. The swelling was related to the electrostatic interactions by infrared spectroscopy and zeta-potential measurements. The stability of the capsules as well as the swelling degree at a given pH could be tuned, when the ionic strength of the medium was altered.     

Stimulated release of small molecules from polyelectrolyte multilayer nanocoatings

Free thiol-containing polyelectrolytes serve simultaneously as a material for self-assembly of a multilayer nanocoating and as a carrier of small molecules for release from the coating in response to an environmental cue.     

Tunable drug release from hydrolytically degradable layer-by-layer thin films

The development of new thin film fabrication techniques that allow for precise control of degradation and drug release properties could represent an important advance in the fields of drug delivery and biomedicine. Polyelectrolyte layer-by-layer (LBL) thin films can be assembled with nanometer scale control over spatial architecture and morphology, yet very little work has focused on the deconstruction of these ordered thin films for controlled release applications. In this study, hydrolytically degradable LBL thin films are constructed by alternately depositing a degradable poly(beta-amino ester) (polymer 1) and a series of model therapeutic polysaccharides (heparin, low molecular weight heparin, and chondroitin sulfate). These films exhibit pH-dependent, pseudo-first-order degradation and release behavior. The highly versatile and tunable properties of these materials make them exciting candidates for the controlled release of a wide spectrum of therapeutics.     

Tripod molecules build molecular networks and open-dimer capsules by weak interactions

Three tripod molecules, tris(2-methoxy-5-nitrobenzyl)phosphine oxide (1), tris(2-butoxy-3-methyl-5-nitrobenzyl)phosphine oxide (2), and tris(3-nitrobenzyl)amine (TNBA), were synthesized and crystallized. The structures of 1, 2, and their comparison (TNBA) were determined by X-ray crystallography. It is noteworthy that compound 1 interacted with adjacent molecules via π-π stacking and C-H···π interactions to yield an open supramolecular network with the porosity P in 8.9%, whereas compound 2 gathered closely...     

Thermoelasticity of weak polyelectrolyte networks

The thermoelastic behavior of poly(vinyl alcohol)–poly(acrylic acid) networks was evaluated in pure water and CaCl₂ solution. The ratio f_e/f of the energy component of the force to the total force, evaluated without taking into account polymer–diluent specific interactions, ranged from ?0.75 for networks swollen in pure water to ?5.7 in 0.1M CaCl₂. However, an analysis based on Flory's theory of polyelectrolyte gels yields f_e/f constant at ?1.32 when specific interactions are accounted for. In addition, the variation of In (r²)₀ with CaCl₂ concentration is 2000 times that with water. In neither pure water nor CaCl₂ solution can specific interactions be neglected.     

Direct determination of the thermodynamics of polyelectrolyte complexation and implications thereof for electrostatic layer-by-layer assembly of multilayer films

Interpolyelectrolyte complex (IPEC) formation between poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) has been studied over a range of ionic strengths by isothermal titration calorimetry (ITC), turbidity titration, and electrostatic layer-by-layer assembly (ELBL). The results indicate that IPEC formation of PSS/PAH in aqueous solution is predominantly entropy-driven. The thermodynamic parameters suggest the formation of different types of complexes and aggregates due to salt-induced conformational changes in the polyelectrolyte conformation. Differences in polyelectrolyte behavior in the different salt-concentration regimes are described in terms of changes in the Debye screening length of the polyelectrolytes. The relationship of the results to the effect of salt concentration on the assembly of polyelectrolyte multilayer films (PEMs) is discussed.     

Salt softening of polyelectrolyte multilayer capsules

The changes in the morphology and the mechanical properties of hollow polyelectrolyte multilayer capsules made from poly(styrenesulfonate)/poly(allylamine hydrochloride) in response to added salt were investigated. We found that capsules shrink in response to salt exposure. The effect depends strongly on the nature of the salt added and follows trends of the Hoffmeister series, with weakly hydrated cations inducing the strongest shrinking. For NaCl, we have investigated additional effects on capsule mechanical properties that are occurring above a 3 M salt concentration and we found that the morphological changes are accompanied by a pronounced softening of the capsule wall material, which we can quantify by analyzing the force response of capsules in the prebuckling regime. This shows that salts can act as plasticizers in the multilayers and induce annealing effects.     

Rapid release of plasmid DNA from polyelectrolyte multilayers: a weak poly(acid) approach

We demonstrate an approach to the assembly of DNA-containing polyelectrolyte multilayers that can be used to promote rapid release of DNA from surfaces. The approach is based on layer-by-layer incorporation of poly(acrylic acid) to promote rapid erosion in physiologically relevant media.     

Photoactivated release of cargo from the cavity of polyelectrolyte capsules to the cytosol of cells

Polyelectrolyte capsules with metal nanoparticles in their walls and fluorescently labeled polymers as cargo inside their cavity were prepared. Capsules were ingested by living cells with no uncontrolled release of the cargo upon the incorporation process. Photoinduced heating of the metal nanoparticles in the capsule walls lead to rupture of the capsule walls, and the polymeric cargo was released to the whole cytosol. Viability tests demonstrate that opening of capsules at moderate light intensities does not impair the cellular metabolism, whereas capsule opening at high light intensities ultimately leads to cell death.