Single-component layer-by-layer weak polyelectrolyte films and capsules: Loading and release of functional molecules

Poly(carboxylic acid) hydrogel films and hollow capsules undergo reversible size changes in response to variations in pH and/or ionic strength. The films and capsules were obtained from hydrogenbonded poly-N-vinylpyrrolidone/poly(carboxylic acid) layer-by-layer films by chemical crosslinking of the polyacid, followed by pH-induced removal of poly-N-vinylpyrrolidone. Surface-attached hydrogel films present attractive matrices for reversible pH-stimulated loading and/or controlled release of large amounts of synthetic or natural macromolecules including proteins. By varying acidity of poly(carboxylic acids), the hydrogel swelling and the corresponding values of pH for encapsulation/release of functional molecules could be tuned in a wide range from pH 5 to 10. In addition, the capsules are capable of entrapping macromolecules by “locking” the capsule wall with an electrostatically associating polycation, followed by the release of the encapsulated macromolecules at high salt concentrations. The text was submitted by the authors in English.     

Reversible pH‐Dependent Properties of Multilayer Microcapsules Made of Weak Polyelectrolytes

Summary: We investigated microcapsules composed of the weak polyelectrolytes poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) assembled on calcium carbonate cores. These capsules are stable in the pH range from 2.5 to 11.5, undergoing reversible swelling in the pH interval from 2.7 to 2.6. Capsule swelling occurs at a protonation degree above 90%. The pH‐dependent size variation of PAH/PMA capsules is blocked after crosslinking of the polyelectrolyte layers.

Schematic of the swelling and de‐swelling of the capsules with changing pH.     

Hollow capsules formed in a single stage via interfacial hydrogen-bonded complexation of methylcellulose with poly(acrylic acid) and tannic acid

Hollow capsules can be prepared in a single stage by the interfacial complexation of methylcellulose (MC) with poly(acrylic acid) (PAA) or tannic acid (TA) via hydrogen bonding in aqueous solutions. The formation of capsules is observed when viscous solution of methylcellulose is added drop-wise to diluted solutions of polyacids under acidic conditions. The optimal parameters such as polymer concentration and solution pH for the formation of these capsules were established in this work. It was found that tannic acid forms capsules in a broader range of concentrations and pHs compared to poly(acrylic acid). The TA/MC capsules exhibited better stability compared to PAA/MC in response to increase in pH: the dissolution of TA/MC capsules observed at pH > 9.5; whereas PAA/MC capsules dissolved at pH > 3.8. The interfacial complexation can be considered as a potential single stage alternative to the formation of capsules using multistage layer-by-layer deposition method.     

Resealing of Polyelectrolyte Capsules after Core Removal

Poly(styrene sulfonate) and poly(allylamine hydrochloride) layers have been adsorbed supplementarily on polyelectrolyte capsules. The permeability of the original capsules consisting of four layer pairs was of the order of 10^–5 m/s for fluorescein. They were also permeable for macromolecules. Polyelectrolyte layers adsorbed afterwards reduced the permeability by three orders of magnitude for small molecules. These findings are interpreted as a resealing of pores, induced by the osmotic stress during fabrication.     

Entrapment of α‐Chymotrypsin into Hollow Polyelectrolyte Microcapsules

Stable hollow polyelectrolyte capsules were produced by the layer‐by‐layer assembling of non‐biodegradable polyelectrolytes – poly(allylamine) and poly(styrenesulfonate) on melamine formaldehyde microcores followed by the core decomposition at low pH. A proteolytic enzyme, α‐chymotrypsin, was encapsulated into these microcapsules with high yields of up to 100%. The encapsulation procedure was based on the protein adsorption onto the capsule shells and on the pH‐dependent opening and closing of capsule wall pores. The protein in the capsules retained a high activity, and thermo‐ and storage stability. The nanostructured polyelectrolyte shell protected the proteinase from a high molecular weight inhibitor. Such enzyme‐loaded capsules can be used as microreactors for biocatalysis.     

Microcapsules made of weak polyelectrolytes: templating and stimuli-responsive properties

Hollow microcapsules composed of the weak polyelectrolytes poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) are templated on silicon oxide particles using the layer-by-layer adsorption. The colloidal template is removed with a buffer system of hydrofluoric acid and ammonium fluoride. With this buffer system, the template can be dissolved in mild pH conditions, where the polymeric layers are still stable. The morphology and the thickness of the resulting capsules are investigated with atomic force microscopy. The resulting hollow capsules show pH-dependent properties. The shells are stable over a broad pH range and swell and immediately dissolve for pH values below 2.3 and above 11. If the molecular weight of the poly(methacrylic acid) is increased, the enhanced entanglement of the polymers results in a reversible swelling of the capsules at low and at high pH. The swelling degree is probed with confocal laser scanning microscopy. In addition to the pH-dependent size variations, the different ionization degree of poly(methacrylic acid) as a function of pH is used for the selective binding of calcium ions.     

pH-responsive capsules derived from nanocrystal templating

In the current work we demonstrate a facile and versatile way to create hydrophilic polymeric capsules by integration of Au nanocrystal templating, surface-initiated atom-transfer radical polymerization, and selective chemical cross-linking of polymer shells. Capsules of the homopolymer of 2-(dimethylamino)ethyl methacrylate and its copolymers with 2-(diethylamino)ethyl methacrylate and poly(ethylene glycol) methyl ether methacrylate were constructed. They swell at low pH and shrink at high pH. On the basis of the pH sensitivity of the resulting capsules, encapsulation and release of a drug model, rhodamine 6G, were realized. Furthermore, by cleaving Au-S bonds between Au cores and polymer shells, capsules containing free Au cores were generated, paving a simple pathway to introduce more functionality to the polymeric capsules.     

Matrix polyelectrolyte microcapsules: new system for macromolecule encapsulation

A new approach to fabricate polyelectrolyte microcapsules is based on exploiting porous inorganic microparticles of calcium carbonate. Porous CaCO3 microparticles (4.5-5.0 microns) were synthesized and characterized by scanning electron microscopy and the Brunauer-Emmett-Teller method of nitrogen adsorption/desorption to get a surface area of 8.8 m2/g and an average pore size of 35 nm. These particles were used as templates for polyelectrolyte layer-by-layer assembly of two oppositely charged polyelectrolytes, poly(styrene sulfonate) and poly(allylamine hydrochloride). Calcium carbonate core dissolution resulted in formation ofpolyelectrolyte microcapsules with an internal matrix consisting of a polyelectrolyte complex. Microcapsules with an internal matrix were analyzed by confocal Raman spectroscopy, scanning electron microscopy, force microscopy, and confocal laser-scanning fluorescence microscopy. The structure was found to be dependent on a number of polyelectrolyte adsorption treatments. Capsules have a very high loading capacity for macromolecules, which can be incorporated into the capsules by capturing them from the surrounding medium into the capsules. In this paper, we investigated the loading by dextran and bovine serum albumin as macromolecules. The amount of entrapped macromolecules was determined by two independent methods and found to be up to 15 pg per microcapsule.     

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.     

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 (PGA(Alk)) 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 PGA(Alk) 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) (PVPON(Alk)) via hydrogen bonding with poly(methacrylic acid) (PMA) and combined this with the aforementioned system (PGA(Alk)/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.     

Stabilization of small unilamellar DMPC-liposomes by uncharged polymers

 Polymer-free and polymer-bearing small unilamellar (SUV) liposomes from dimyristoyl-phosphatidylcholine (DMPC) were prepared under standardized conditions. Polymer-bearing liposomes were formed by incorporating an uncharged polymer [hydrolyzed poly(vinyl alcohol) (PVA), poly(vinyl alcohol-co-vinylacetal) (PVA-Al), poly(vinyl alcohol-co-vinyl propional) (PVA-Prol) poly(vinyl alcohol-co-vinyl butiral) (PVA-Bul) copolymer or poly(vinyl pyrrolidone) (PVP)] into the membrane bilayer of vesicles. The kinetic (long-term) stability of the liposome dispersions stored in distilled water, in physiological NaCl solution and at various pH values, respectively, were studied. The physical stability of vesicles was tested by measuring the size and the zeta potential of liposomes by means of a Malvern Zetasizer 4 apparatus. It was shown that most of these polymers are effective steric stabilizers for the DMPC-liposomes. Among the polymers, the PVA-Bul and PVA-Prol copolymers and the PVP of high molecular mass exhibited the most efficient stabilizing effect at each pH studied, indicating that the formation of a relatively thick polymer layer around the lipid bilayers ensures an enhanced and prolonged physical stability of liposomes. Also, the butiral or propional side chain in the PVA-based copolymers presumably promotes the anchoring of macromolecules to the vesicles. Using these macromolecules, the colloidal interactions between vesicles can be modified and so the physical stability of liposomes and the kinetic stability of liposome dispersions can also be controlled. Received: 20 May 1997 Accepted: 03 September 1997     

Macromolecule mediated bioinspired silica synthesis using a diol-modified silane precursor

Following recent investigations on the role of synthetic and biological macromolecules in silicification and biosilicification, we report here the bioinspired synthesis of silica structures under ambient conditions and neutral pH mediated by two synthetic macromolecules. In this research ethylene glycol modified silane (EGMS) was used as the silica precursor. The macromolecules used were either poly(allylamine hydrochloride) (PAH) or poly-l-lysine (PLL), both being cationically charged at neutral pH in an aqueous medium. Mild conditions that constitute the bioinspired or biomimetic synthesis were used to compare the behaviour of the EGMS to other silica precursors. The products were characterised by Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS) and Fourier Transform Infrared Spectroscopy (FTIR). The formation of well-defined spherical silica particles (for both PAH and PLL) and hexagons (for PLL only), was shown by electron microscopy. In addition, it was also found that these macromolecules were incorporated into the silica products, thus fulfilling the dual role of catalysts and structure directing agents in a similar fashion to that described in the literature for the formation of (bio)silica, as facilitated by (bio)macromolecules.This paper is dedicated to Mike Owen on occasion of his winning the DeBruyn medal, the first silicon chemist to do so.     

pH-responsive protein microcapsules fabricated via glutaraldehyde mediated covalent layer-by-layer assembly

Bovine serum albumin (BSA) hollow microcapsules were fabricated through glutaraldehyde (GA) mediated covalent layer-by-layer assembly. The GA cross-linking of the adsorbed BSA on the colloidal particles enabled their surfaces to be covered by reactive aldehyde groups, which reacted with BSA molecules to result in another covalently linked layer. Repeating of this cycle could then yield particles coated with BSA multilayers. Hollow microcapsules well dispersed in water were obtained after core removal. The good integrity and morphology of the BSA capsules were confirmed and characterized by confocal laser scanning microscopy, scanning electron microscopy and scanning force microscopy. The obtained BSA microcapsules possess reversible pH response, i.e., the capsules are permeable to macromolecules below pH 4 or above pH 10, while impermeable in between. The mechanisms of permeability transition were discussed. Using this property, dextran, with a molecular weight of ~155 kDa, was successfully loaded.     

Synthesis of thermo- and pH-sensitive star-shaped poly(2-alkyl-2-oxazoline) and its properties in aqueous its properties in aqueous solutions with varying medium acidity

Abstract

pH-sensitive eight-arm star-shaped polymer with calix[8]arene core and block copolymer of poly(2-methoxycarbonylethyl-2-oxazoline) and poly(2-isopropyl-2-oxazoline) arms was synthesized for the first time. The block composition was 1:1 and molar mass was 24000?g?mol^?1. The behavior of synthesized star in aqueous solutions was analyzed by turbidity and light scattering at the pH values from 2 to 12.2. It is shown that in an organic solvent, the polymer molecule has a low shaped asymmetry. In aqueous solutions, the synthesized star exhibits thermosensitivity with a lower critical solution temperature. It was found that at low temperature in solutions, there were macromolecules and aggregates which were formed due to interaction of hydrophobic cores. The phase separation temperatures did not depend on pH in basic media and decreased strongly at pH <5.     

Molecular properties of poly(carboxybetaine) in solutions with different ionic strengths and pH values

Viscometry and dynamic and static light scattering are employed to study the molecular properties of water-soluble poly(carboxybetaine), that is, poly(2-(diallyl(methyl)ammonium) acetate). It is shown that, in solutions with pH 1, the polymer behaves as a polyelectrolyte. In media with pH 6 and 13, an increase in the concentration of sodium chloride increases the intrinsic viscosity of the polymer and the hydrodynamic radius of its macromolecules, thereby indicating the antipolyelectrolyte effect typical of polymer zwitterions. In water and 0.1 M NaOH, the second virial coefficient of the polymer is close to zero, while exponent ν, which relates the sizes of macromolecules to their molecular masses, is 0.5. In 1 M NaCl, the second virial coefficient becomes positive, while exponent increases to 0.58. The Kuhn segment lengths of poly(carboxybetaine) molecules are 6.3 and 6.6 nm in water and 1 M NaCl, respectively. An increase in the hydrodynamic radius of macromolecules with the ionic strength of the solution is due to the shielding of attraction between zwitterions belonging to polybetaine monomer units located far apart along a macromolecular chain.     

Capsules with Silver Nanoparticle Enrichment Subdomains and Their Antimicrobial Properties

The fabrication of polyelectrolyte multilayer capsules with controllable submicron‐sized subdomains and the in situ synthesis of silver nanoparticles are reported. Because poly(acrylic acid) (PAA) is released from the shell of the capsules in the dissolution process of sacrificial cores, the remaining poly(4‐vinylpyridine) (PVP) forms subdomains of spheres with controllable sizes, which can be tuned by the number of PVP/PAA bilayers. This creates capsules with special surface morphology and enables the in situ synthesis of Ag nanoparticles within the PVP subdomains on the shell of capsules. In addition, the in‐situ formed Ag nanoparticles can be mostly released from PVP subdomains of capsules in pH 2.0 solution, whereas they are stable in neutral solution. These specially designed capsules containing Ag nanoparticles can be used as antimicrobial materials and potentially benefit remote drug release by laser activation.     

胶束增强型聚电解质胶囊的结构研究

研究了胶束增强型聚电解质(PAH/PSS和PADA/PSS)胶囊在不同溶液环境中的形貌变化,发现这种新型的胶囊具有迥异于传统聚电解质胶囊的囊壁结构;研究了二维聚电解质复合膜与模板溶解液中嵌段共聚物PS-b-PAA胶束之间的相互作用,发现胶束层可以通过静电力与聚电解质胶囊囊壁相互作用.同时,模拟模板溶出后聚电解质胶囊内部的环境条件,研究了嵌段共聚物胶束在胶囊内部的存在状态及其在透析过程中的变化规律,认为共聚物可以通过疏水作用沉积于聚电解质复合膜的内壁,并通过Ca2+离子的桥联作用稳定,也就是在聚电解质复合膜层基础上又形成了一层胶束层.即这种胶束增强型聚电解质微胶囊的囊壁是由聚电解质层和胶束层所形成的双层结构.用这种双层结构模型,我们合理解释了胶囊在高盐离子浓度下的形貌变化.     

Matrix polyelectrolyte capsules based on polysaccharide/MnCO₃ hybrid microparticle templates

An efficient strategy for biomacromolecule encapsulation based on spontaneous deposition into polysaccharide matrix-containing capsules is introduced in this study. First, hybrid microparticles composed of manganese carbonate and ionic polysaccharides including sodium hyaluronate (HA), sodium alginate (SA) and dextran sulfate sodium (DS) with narrow size distribution were synthesized to provide monodisperse templates. Incorporation of polysaccharide into the hybrid templates was successful as verified by thermogravimetric analysis (TGA) and confocal laser scanning microscopy (CLSM). Matrix polyelectrolyte microcapsules were fabricated through layer-by-layer (LbL) self-assembly of oppositely charged polyelectrolytes (PEs) onto the hybrid particles, followed by removal of the inorganic part of the cores, leaving polysaccharide matrix inside the capsules. The loading and release properties of the matrix microcapsules were investigated using myoglobin as a model biomacromolecule. Compared to matrix-free capsules, the matrix capsules had a much higher loading capacity up to four times; the driving force is mostly due to electrostatic interactions between myoglobin and the polysaccharide matrix. From our observations, for the same kind of polysaccharide, a higher amount of polysaccharide inside the capsules usually led to better loading capacity. The release behavior of the loaded myoglobin could be readily controlled by altering the environmental pH. These matrix microcapsules may be used as efficient delivery systems for various charged water-soluble macromolecules with applications in biomedical fields.     

Spontaneous change in thermosensitive properties of aqueous solutions of poly(<Emphasis Type="Italic">N,N</Emphasis>-dimethylaminoethyl methacrylate) and its mixtures with sodium dodecyl sulfate

It is shown that the properties of aqueous solutions of poly(N,N-dimethylaminoethyl methacrylate) are unstable over time: the pH value spontaneously decreases, the phase separation temperature grows, and the light scattering ability of dispersions arising above the said temperature weakens. These effects are enhanced after dilution of solutions, become less pronounced with an increase in pH, and disappear when the solutions are isolated from atmosphere (under argon). It is inferred that the lability of the indicated properties is associated with acidification of polymer solutions due to their interaction with air carbon dioxide and the enhancement of protonation of macromolecules. Potentiometric and tensiometric measurements have demonstrated that upon introduction of sodium dodecyl sulfate into solutions of poly(N,N-dimethylaminoethyl methacrylate), the surfactant-polymer interaction slows down owing to a spontaneous increase in the charging of macromolecules in the course of time.     

Preparation of silica capsules via an acid-catalyzed sol–gel process in inverse miniemulsions

Silica capsules were prepared via a sol–gel process using tetraethyl orthosilicate (TEOS) in inverse miniemulsions under highly acidic conditions (pH?<?2). Formation of silica capsules under acidic conditions proceeded via internal phase separation of silica species in the droplets. This mechanism is different from the well-known interfacial reaction mechanism for most syntheses of silica capsules. The driving force for the formation of capsules was the interaction between silica species and cetyltrimethylammonium bromide (CTAB) as well as between silica species and the hydrophilic block of the block copolymer surfactant, poly(ethylene-co-butylene)-b-poly(ethylene oxide) (P(E/B)-PEO). The effects of synthetic parameters on the particle morphology and size were systematically investigated in terms of the reaction time, amount of TEOS, CTAB, P(E/B)-PEO, and hydrochloric acid concentration, as well as addition of ethanol.