pH-responsive properties of hollow polyelectrolyte microcapsules templated on various cores

Hollow polyelectrolyte microcapsules made of poly(allylamine hydrochloride) and sodium poly(styrene sulfonate), templated on various cores, manganese and calcium carbonate particles or polystyrene latexes, were investigated. The polyelectrolyte multilayers respond to a change of pH, leading to a swelling of the capsules in basic conditions and a further shrinking when the pH is reduced to acidic. The nature of the core and the subsequent dissolution process have an influence on this pH responsiveness, and the structuring effect of tetrahydrofuran on the multilayers has been demonstrated. Increasing the molecular weight of the polymers or the number of layers causes also a rigidification of the structure and modifies the pH response.     

Charge-controlled permeability of polyelectrolyte microcapsules

Multilayer microcapsules showing unique charge-controlled permeability have been successfully fabricated by employing poly(styrene sulfonate) (PSS)-doped CaCO3 particles as templates. Encapsulation of the PSS molecules is thus achieved after core removal. Scanning force microscopy (SFM), UV-vis, Raman spectroscopy, and zeta-potential confirm the existence of the PSS molecules in the CaCO3 particles and the resultant microcapsules, which are initially incorporated during the core fabrication process. A part of these additionally introduced PSS molecules interacts with PAH molecules residing on the inner surface of the multilayer wall to form a stable complex, while the other part is intertwined in the capsule wall or in a free state. Capsules with this structure possess many special features, such as highly sensitive permeability tuned by probe charge and environmentally controlled gating. They can completely reject negatively charged probes, but attract positively charged species to form a higher concentration in the capsule interior, as evidenced by confocal microscopy. For example, the capsules completely exclude dextran labeled with fluorescein isothiocyanate (FITC-dextran), but are permeable for dextran labeled with tetramethylrhodamine isothiocyanate (TRITC-dextran) having similar molecular mass (from 4 to 70 kDa), although there are only few charged dyes in a dextran chain. By reversing the charge of the probes through pH change, or by suppressing charge repulsion through salt addition, the permeation can be readily switched for proteins such as albumin or small dyes such as fluorescein sodium salt.     

Elasticity of polyelectrolyte multilayer microcapsules

We present a novel approach to probe elastic properties of polyelectrolyte multilayer microcapsules. The method is based on measurements of the capsule load-deformation curves with the atomic force microscope. The experiment suggests that at low applied load deformations of the capsule shell are elastic. Using elastic theory of membranes we relate force, deformation, elastic moduli, and characteristic sizes of the capsule. Fitting to the prediction of the model yields the lower limit for Young's modulus of the polyelectrolyte multilayers of the order of 1-100 MPa, depending on the template and solvent used for its dissolution. These values correspond to Young's modulus of an elastomer.     

Thermoreversible crosslinking of polyelectrolyte chains

Thermoreversible crosslinking of polyelectrolyte chains via short-range attractions such as hydrogen bonding induced by uncharged or charged particles is studied within the Flory model of ideal association. Electrostatic interactions between the charges at different linking fractions are taken into account by using a generalized random phase approximation approach which includes the network connectivity. We find that at certain concentration of linking agents an infinitely large polymer network is formed. We calculate the structural gelation lines for linkers of different charges and functionalities.     

Assembly and mechanical properties of phosphorus dendrimer/polyelectrolyte multilayer microcapsules

We report the preparation, characterization, and mechanical properties of polyelectrolyte/phosphorus dendrimer multilayer microcapsules. The shells of these microcapsules are composed either by alternating poly(styrenesulfonate) (PSS) and positively charged dendrimer G4(NH+Et2Cl-)96 or by alternating poly(allylamine hydrochloride) (PAH) and negatively charged dendrimer G4(CH-COO-Na+)96. The same multilayers were constructed on planar support to examine their layer-by-layer growth and to measure the multilayer thickness. Surface plasmon resonance spectroscopy (SPR) showed regular linear growth of the assembly upon each bilayer deposited. We probe the mechanical properties of these polyelectrolyte/dendrimer microcapsules by measuring force-deformation curves with the atomic force microscope (AFM). The experiment suggests that they are much softer than PSS/PAH microcapsules studied before. This softening is attributed to an enhanced permeability of the polyelectrolyte/dendrimer multilayer shells as compared with multilayers formed by linear polyelectrolytes. In contrast, Young's modulus of both dendrimer-based multilayers was found to be on the same order as that of PSS/PAH multilayers.     

Salt softening of polyelectrolyte multilayer microcapsules

By using a combination of atomic force and confocal microscopy, we explore the effect of 1:1 electrolyte (NaCl) on the stiffness of polyelectrolyte microcapsules. We study the "hollow" and "filled" (with polystyrene sulfonate) capsules. In both cases the shells are composed of layers of alternating polystyrene sulfonate (PSS) and polyallylamine hydrochloride (PAH). The stiffness of both "hollow" and "filled" capsules was found to be largest in water. It decreases with salt concentration up to approximately 3 mol/L and gets quasi-constant in more concentrated solutions. The "filled" capsules are always stiffer than "hollow." The observed softening correlates with the salt-induced changes in morphology of the multilayer shells detected with the scanning electron microscopy. It is likely that at concentrations below approximately 3 mol/L the multilayer shell is in a "tethered" state, so that the increase in salt concentration leads to a decrease in number of ionic cross-links and, as a result, in the stiffness. In contrast, above the critical concentration of approximately 3 mol/L multilayer shells might be in a new, "melted," state. Here the multilayer structure is still retained, but sufficient amount of ionic cross-links is broken, so that further increase in salt concentration does not change the capsule mechanics. These ideas are consistent with a moderate swelling of multilayers at concentrations below approximately 3 mol/L and significant decrease in their thickness in more concentrated solutions measured with surface plasmon spectroscopy.     

Light-responsive polyelectrolyte/gold nanoparticle microcapsules

We report the preparation and characterization of light-responsive delivery vehicles, microcapsules composed of multiple polyelectrolyte layers and light-absorbing gold nanoparticles. The nanostructured capsules were loaded with macromolecules (fluorescein isothiocyanate-labeled dextran) by exploiting the pH-dependence of the shell permeability, and the encapsulated material was released on demand upon irradiation with short (10 ns) laser pulses in the near-infrared (1064 nm). In addition, the polyelectrolyte multilayer shell was modified with lipids (dilauroylphosphatidylethanolamine) and then functionalized with ligands (monoclonal immunoglobulin G antibodies) for the purposes of enhanced stability and targeted delivery, respectively. We anticipate that these capsules will find application in a range of areas where controlled delivery is desirable.     

Formation of microcapsules from polyelectrolyte and covalent interactions

A new approach combining electrostatic and covalent bonds was established for the formation of resistant capsules with long-term stability under physiological conditions. Three kinds of interactions were generated in the same membrane: (1) electrostatic bonds between alginate and poly-L-lysine (PLL), (2) covalent bonds (amides) between propylene-glycol-alginate (PGA) and PLL, and (3) covalent bonds (amides) between BSA and PGA. Down-scaling of the capsules size (< or =1 mm diameter) with a jet break-up technology was achieved by modifying the rheological properties of the polymer solution. Viscosity of the PGA solution was reduced by 95% with four successive pH stabilizations (pH 7), while filtration (0.2 microm) and sterilization was possible. Covalent bond formation was initiated by addition of NaOH (pH 11) using a transacylation reaction. Kinetics of the chemical reaction (pH 11) were simulated by two mathematical models and adapted in order to preserve immobilization of animal cells. It was demonstrated that diffusion of NaOH in the absence of BSA resulted in gelation of 94% of the bead and death of 94% of the cells after 10 s reaction. By addition of BSA only 46% of the cells were killed within the same reaction time (10 s). Mechanical resistance of this new type of capsule could be increased 5-fold over the standard polyelectrolytic system (PLL-alginate). Encapsulated CHO cells were successfully cultivated for 1 month in a repetitive batch mode, with the mechanical resistance of the capsules decreasing by only 10% during this period. The combination of a synthetic and natural protein resulted in enhanced stability toward culture medium and proteolytic enzymes (250%).     

Biofunctionalization of polyelectrolyte microcapsules with biotinylated polyethylene glycol-grafted liposomes

Hollow polyelectrolyte microcapsules (PEMC) are prepared using layer-by-layer self-assembly of polyelectrolytes on melamine formaldehyde templates, followed by template dissolution, and subsequent coating with biotinylated polyethylene glycol-grafted liposomes. These potential site-specific carrier systems show a high specificity for NeutrAvidin binding and a strong resistance against unspecific protein binding. It is concluded that this design with NeutrAvidin as the outermost layer of such capsules provides an ideal platform for the biofunctionalization of PEMC as drug delivery systems or as artificial cell-like structures for biomimetic studies.     

Controlled rupture of magnetic polyelectrolyte microcapsules for drug delivery

In this study, a magnetic-sensitive microcapsule was prepared using Fe 3O 4/poly(allylamine) (Fe 3O 4/PAH) polyelectrolyte to construct the shell. Structural integrity, microstructural evolution, and corresponding release behaviors of fluorescence dyes and doxorubicin were systematically investigated. Experimental observations showed that the presence of the magnetic nanoparticles in the shell structure allowed the shell structure to evolve from nanocavity development to final rupture of the shell under a given magnetic stimulus of different time durations. Such a microstructural evolution of the magnetic sensitive shell structure explained a corresponding variation of the drug release profile, from relatively slow release to burst-like behavior at different stages of stimulus. It has proposed that the presence of magnetic nanoparticles produced heat, due to magnetic energy dissipation (as Brown and Neel relaxations), and mechanical vibration and motion that induced stress development in the thin shell. Both mechanisms significantly accelerated the relaxation of the shell structure, causing such a microstructural evolution. With such a controllable microstructural evolution of the magnetic-sensitive shell structure, active substances can be well-regulated in a manageable manner with a designable profile according to the time duration under magnetic field. A cell culture study also indicated that the magnetic-sensitive microcapsules allowed a rapid uptake by the A549 cell line, a cancerous cell line, suggesting that the magnetic-sensitive microcapsule with controllable rupturing behavior of the shell offers a potential and effective drug carrier for anticancer applications.     

Synthesis of silver nanoparticles for remote opening of polyelectrolyte microcapsules

Silver nanoparticles of 10, 18, and 23 nm were synthesized in aqueous medium by chemical reduction of silver nitrate in excess of sodium borohydride. Modification of polyelectrolyte shells with synthesized silver nanoparticles was performed using the layer-by-layer approach. Remote opening of the polyelectrolyte/silver capsules was performed with a CW Nd:YAG FD laser with an average incident power output up to 70 mW. Capsules with a mixture of 10 and 18 nm silver nanoparticles in its polyelectrolyte shell were ruptured after less than 7 s of laser irradiation, while microcapsules with 23 nm silver nanoparticles in the shell were broken after 11 s of laser treatment and 10 nm silver nanoparticles were broken after 26 s.     

Effect of pH and salt on the stiffness of polyelectrolyte multilayer microcapsules

By using a combination of atomic force and confocal microscopy, we explore the effect of pH and salt on the stiffness of polyelectrolyte microcapsules with shells composed of strong polyanions and weak polycations. The stiffness of the capsules was found to be largest in water. It decreases slightly with added salt and gets much smaller both in acidic and in alkaline solutions. The moderate softening of the capsules in electrolyte solutions indicates that even high salt concentration does not significantly dissociate polyelectrolytes in the multilayer. The dramatic softening of the capsules at high pH probably reflects a decrease in the charge density of a polycation, which leads to a reduction in the number of ionic cross-links. In contrast, low stiffness of the capsules in acidic solutions seems to be connected mostly with the enhanced permeability of the multilayer shell.     

Hepatic-targeting microcapsules construction by self-assembly of bioactive galactose-branched polyelectrolyte for controlled drug release system

We describe the construction of hepatic-targeting microcapsules by self-assembly of chemo-enzymatic synthesized poly(vinyl galactose ester-co-methacryloxyethyl trimethylammonium chloride) (PGEDMC) containing galactose branches, which can be specifically recognized by membrane bound galactose receptors (ASGPR), for acyclovir (ACV) controlled release system. Alternate deposition of PGEDMC and poly(sodium 4-styrenesulfonate) (PSS) was carried out on ACV microcrystals. It was revealed that the drug release rate decreases with the increase of coated layer number and a microcapsule-drying treatment would enhance the sustained release effect probably because of a multilayer shrink and tightness during the process. The complete release of ACV yielded a hollow PGEDMC/PSS multilayered network with favorable integrity and nano-thickness by TEM and SEM. The potential targetability of the system was proved in vitro by PNA lectin recognition. Lectin hardly adsorbed on the film where the outmost layer was a polyanion or a polycation without galactose component. Whilst the galactose-containing layer (PGEDMC) was the outmost layer, a significant lectin combination was observed. This technique could provide a promising way to encapsulate and deliver various target substances in biological and pharmaceutical applications.     

A 'microfluidic pinball' for on-chip generation of Layer-by-Layer polyelectrolyte microcapsules

Inspired by the game of "pinball" where rolling metal balls are guided by obstacles, here we describe a novel microfluidic technique which utilizes micropillars in a flow channel to continuously generate, encapsulate and guide Layer-by-Layer (LbL) polyelectrolyte microcapsules. Droplet-based microfluidic techniques were exploited to generate oil droplets which were smoothly guided along a row of micropillars to repeatedly travel through three parallel laminar streams consisting of two polymers and a washing solution. Devices were prototyped in PDMS and generated highly monodisperse and stable 45±2 μm sized polyelectrolyte microcapsules. A total of six layers of hydrogen bonded polyelectrolytes (3 bi-layers) were adsorbed on each droplet within <3 minutes and a fluorescent intensity measurement confirmed polymer film deposition. AFM analysis revealed the thickness of each polymer layer to be approx. 2.8 nm. Our design approach not only provides a faster and more efficient alternative to conventional LbL deposition techniques, but also achieves the highest number of polyelectrolyte multilayers (PEMs) reported thus far using microfluidics. Additionally, with our design, a larger number of PEMs can be deposited without adding any extra operational or interfacial complexities (e.g. syringe pumps) which are a necessity in most other designs. Based on the aforementioned advantages of our device, it may be developed into a great tool for drug encapsulation, or to create capsules for biosensing where deposition of thin nanofilms with controlled interfacial properties is highly required.     

Magnetic switch of permeability for polyelectrolyte microcapsules embedded with Co@Au nanoparticles

We explored using a magnetic field to modulate the permeability of polyelectrolyte microcapsules prepared by layer-by-layer self-assembly. Ferromagnetic gold-coated cobalt (Co@Au) nanoparticles (3 nm diameter) were embedded inside the capsule walls. The final 5 mum diameter microcapsules had wall structures consisting of 4 bilayers of poly(sodium styrene sulfonate)/poly(allylamine hydrochloride) (PSS/PAH), 1 layer of Co@Au, and 5 bilayers of PSS/PAH. External alternating magnetic fields of 100-300 Hz and 1200 Oe were applied to rotate the embedded Co@Au nanoparticles, which subsequently disturbed and distorted the capsule wall and drastically increased its permeability to macromolecules like FITC-labeled dextran. The capsule permeability change was estimated by taking the capsule interior and exterior fluorescent intensity ratio using confocal laser scanning microscopy. Capsules with 1 layer of Co@Au nanoparticles and 10 polyelectrolyte bilayers are optimal for magnetically controlling permeability. A theoretical explanation was proposed for the permeability control mechanisms. "Switching on" of these microcapsules using a magnetic field makes this method a good candidate for controlled drug delivery in biomedical applications.     

Equilibrium distribution of permeants in polyelectrolyte microcapsules filled with negatively charged polyelectrolyte: the influence of ionic strength and solvent polarity

The effects of ionic strength and solvent polarity on the equilibrium distribution of fluorescein (FL) and FITC-dextran between the interior of polyelectrolyte multilayer microcapsules filled with negatively charged strong polyelectrolyte and the bulk solution were systematically investigated. A negatively charged strong polyelectrolyte, poly(styrene sulfonate) (PSS), used for CaCO3 core fabrication, was entrapped inside the capsules. Due to the semipermeability of the capsule wall, a Donnan equilibrium between the inner solution within the capsules and the bulk solution was created. The equilibrium distribution of the negatively charged permeants was investigated by means of confocal laser scanning microscopy as a function of ionic strength and solvent polarity. The equilibrium distribution of the negatively charged permeants could be tuned by increasing the bulk ionic strength to decrease the Donnan potential. Decreasing the solvent polarity also could enhance the permeation of FL, which induces a sudden increase of permeation when the ethanol volume fraction was higher than 0.7. This is mainly attributed to the precipitation of PSS. A theoretical model combining the Donnan equilibrium and Manning counterion condensation was employed to discuss the results.     

Activity of immobilized trypsin in the layer structure of polyelectrolyte microcapsules (PEMC)

Polyelectrolyte microcapsules composed by using the LbL technique on stabilized RBC as templates were coated with up to ten layer pairs of trypsin/PSS or trypsin/alginate. The trypsin layer growth was confirmed by particle electrophoresis, confocal laser scanning microscopy, flow cytometry, and protein determination according to Lowry. In the coating series with trypsin/PSS, the amount of immobilized enzyme was larger than that with trypsin/alginate. The enzyme immobilization led to activity reduction of up to 90% compared to that of the same enzyme amount in the solution. No significant differences between the activities of trypsin immobilized in combination with PSS and with alginate were found.     

Influence of the temperature on polyelectrolyte microcapsules: Light scattering and confocal microscopy data

The influence of heating on polyelectrolyte (PE) microcapsules consisting of an even or uneven number of alternating layers of poly(allylamine) and poly(styrenesulfonate) is investigated by the light scattering and confocal microscopy techniques. In the formation of PE microcapsules, CaCO₃ microspherulites are used as “core” dispersed particles. It is established that the capsules decrease in size with increasing temperature and time of heating, irrespective of whether they consist of an even or uneven number of layers. The sensitivity of PE microcapsules to heat is estimated in terms of the activation energy of changes in parameters of their initial structure on heating. It is shown that PE microcapsules consisting of an uneven number of layers are more sensitive to heating as compared to those consisting of an even number of layers. A plausible mechanism is proposed for changes in structure parameters of the microcapsules on heating.     

Influence of chemical shell structure on the thermal properties of microcapsules containing a flame retardant agent

Microcapsules containing ammonium phosphate as the acid source for an intumescent system were prepared by various processes. The microcapsules have different morphologies, load content and various types of polymeric shell. The polymers for our microcapsule shell are polymers considered as carbon source for intumescent formulations. In this paper we discuss the influence of polymeric shell and phosphate content of the microcapsules on the capacity to produce a thermally stable residue at high temperature, one of the characteristics for an intumescent formulation.     

Study of the polyelectrolyte properties of humic acids by conductimetric titration

Solutions of humic acids were titrated with potassium, sodium, lithium, calcium and barium hydroxide using conductimetry. A marked difference was observed in the shape of the curves for alkali metal hydroxides and those for alkaline earth metal hydroxides. From a careful analysis of the measured conductivities, it appears that monovalent cations are hardly bound by the humate polyion, hwereas divalent counter ions show an extremely strong interaction. The latter feature may be fruitfully utilized in quantitative analysis. The conductance properties of humic acids are basically different from those of a linear polyelectrolyte such as polymethacrylate.