Bogdan Parakhonskiy

Colloidal micro- and nano-particles as templates for polyelectrolyte multilayer capsules.

Colloidal particles play an important role in various areas of material and pharmaceutical sciences, biotechnology, and biomedicine. In this overview we describe micro- and nano-particles used for the preparation of polyelectrolyte multilayer capsules and as drug delivery vehicles. An essential feature of polyelectrolyte multilayer capsule preparations is the ability to adsorb polymeric layers onto colloidal particles or templates followed by dissolution of these templates. The choice of the template is determined by various physico-chemical conditions: solvent needed for dissolution, porosity, aggregation tendency, as well as release of materials from capsules. Historically, the first templates were based on melamine formaldehyde, later evolving towards more elaborate materials such as silica and calcium carbonate. Their advantages and disadvantages are discussed here in comparison to non-particulate templates such as red blood cells. Further steps in this area include development of anisotropic particles, which themselves can serve as delivery carriers. We provide insights into application of particles as drug delivery carriers in comparison to microcapsules templated on them.

Anticancer drug delivery system based on calcium carbonate particles loaded with a photosensitizer.

In photodynamic therapy (PDT), photosensitizers are required to arrive in high concentrations at selective targets like cancer cells avoiding toxicity in healthy tissue. In this work, we propose the application of porous calcium carbonate carriers in the form of polycrystalline vaterite for this task. We investigated the loading efficiency for the photosensitizer Photosens in vaterite micro- and nanocarriers. A possible release mechanism depending on the surrounding pH was studied, showing a fast degradation of the carriers in buffers below pH7. These results hold out the prospect of a novel PDT drug delivery system. Variation of particle size or additional coatings allow custom-design of workload release curves. An intrinsic cancer-sensitivity can be expected from the pH-dependent release in the acidic microenvironment of cancer tissue.

Polyelectrolyte multilayer microcapsules templated on spherical, elliptical and square calcium carbonate particles

Recent studies have revealed that a variety of shaped particles can interact with cells in a different way. Elongated particles can be effectively and quickly internalized intercellularly compared with other configurations. Herein we present the potential of fabrication of anisotropic polyelectrolyte multilayer capsules formed by coating spherical, ellipsoid-like and square calcium carbonate (CaCO3) particles. By varying the intermixing speed, time, pH value and ratio of initial ingredients during precipitation such CaCO3 templates are produced. Particles loaded with FITC-dextran and coated with polyelectrolytes could maintain the templated shape after core removal. Quantitative data are derived from analysis of confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) measurements.

Nanoplasmonic Chitosan Nanofibers as Effective SERS Substrate for Detection of Small Molecules

The use of surface enhanced Raman spectroscopy (SERS) is limited by low reproducibility and uniformity of the response. Solving these problems can turn the laboratory use of SERS into real-world application. In this regard, soft SERS-active substrates can enable portable instrumentation and reduce costs in the fabrication of SERS-based sensors. Here, plasmonic free-standing films made of biocompatible chitosan nanofibers and gold nanoparticles are engineered by a simple protocol varying the concentration of chloroauric acid. The concentration and distribution of gold nanoparticles in films are controlled in a predictable way, and SERS spectra for the standard 2-naphthalenethiol with concentration less than 10(-15) M are acquired in a reproducible way. The statistical analysis reveals a relatively high and locally uniform performance of SERS with an enhancement factor of 2 × 10(5) for 86% of the points on the imaged area of the SERS substrate. Potential SERS detection of small molecules, both Rhodamine 6G and d-Glucose, in the micromolar range is demonstrated.

The influence of the size and aspect ratio of anisotropic, porous CaCO3 particles on their uptake by cells

BackgroundRecent reports highlighting the role of particle geometry have suggested that anisotropy can affect the rate and the pathway of particle uptake by cells. Therefore, we investigate the internalization by cells of porous calcium carbonate particles with different shapes and anisotropies.ResultsWe report here on a new method of the synthesis of polyelectrolyte coated calcium carbonate particles whose geometry was controlled by varying the mixing speed and time, pH value of the reaction solution, and ratio of the interacting salts used for particle formation. Uptake of spherical, cuboidal, ellipsoidal (with two different sizes) polyelectrolyte coated calcium carbonate particles was studied in cervical carcinoma cells. Quantitative data were obtained from the analysis of confocal laser scanning microscopy images.ConclusionsOur results indicate that the number of internalized calcium carbonate particles depends on the aspect ratio of the particle, whereby elongated particles (higher aspect ratio) are internalized with a higher frequency than more spherical particles (lower aspect ratio). The total volume of internalized particles scales with the volume of the individual particles, in case equal amount of particles were added per cell.

Macromolecule Loading into Spherical, Elliptical, Star-Like and Cubic Calcium Carbonate Carriers

We fabricated calcium carbonate particles with spherical, elliptical, star-like and cubical morphologies by varying relative salt concentrations and adding ethylene glycol as a solvent to slow down the rate of particle formation. The loading capacity of particles of different isotropic (spherical and cubical) and anisotropic (elliptical and star-like) geometries is investigated, and the surface area of such carriers is analysed. Potential applications of such drug delivery carriers are highlighted.

Hollow polypyrrole containers with regulated uptake/release properties.

Polypyrrole microcontainers were successfully prepared by electrochemical polymerization of pyrrole on the surface of stainless steel electrodes. The size of the nanocontainers and the thickness of the polypyrrole shell (up to complete filling of the container with grown polypyrrole) can be varied by changing both the scan speed of the electrode potential and potential range. Polypyrrole surfaces with high redox current due to their increased surface area are obtained; for optimized conditions, also microcontainers are obtained. The polypyrrole microcontainers with a size of less than 20 microm can be easily detached from the electrode surface and polypyrrole films during several minutes of sonication in an ultrasonic bath. The polypyrrole shell of the microcontainers exhibits very strong barrier properties in acidic media at 27, providing effective encapsulation of low molecular weight species at low pH values.

Tailored intracellular delivery via a crystal phase transition in 400 nm vaterite particles

Porous vaterite containers of 400 nm size are studied with respect to intracellular drug delivery applications. A generic crystal phase transition from vaterite to calcite serves as a novel payload release mechanism, which reveals a delayed burst-release. This will permit control of the pharmacokinetics allowing for applications like preventive drug administration or scheduled application of pharmaceuticals during long term therapy. Experiments with two types of payloads, providing different molecular weights and zeta-potentials, demonstrate a flexible way of tailoring the payload delivery time via the molecular properties of the cargo. A dual in vitro cellular uptake experiment with human ovarian carcinoma cells ES2 and human fibroblasts MRC5 shows no cytotoxicity, no influence on cell viability, and fast penetration of substance-loaded containers into cells. Flow cytometry analysis proves high uptake rates and 3D microscopy analysis reveals the intracellular distribution.

Composite Magnetite and Protein Containing CaCO3 Crystals. External Manipulation and Vaterite → Calcite Recrystallization-Mediated Release Performance

Biocompatibility and high loading capacity of mesoporous CaCO3 vaterite crystals give an option to utilize the polycrystals for a wide range of (bio)applications. Formation and transformations of calcium carbonate polymorphs have been studied for decades, aimed at both basic and applied research interests. Here, composite multilayer-coated calcium carbonate polycrystals containing Fe3O4 magnetite nanoparticles and model protein lysozyme are fabricated. The structure of the composite polycrystals and vaterite → calcite recrystallization kinetics are studied. The recrystallization results in release of both loaded protein and Fe3O4 nanoparticles (magnetic manipulation is thus lost). Fe3O4 nanoparticles enhance the recrystallization that can be induced by reduction of the local pH with citric acid and reduction of the polycrystal crystallinity. Oppositely, the layer-by-layer assembled poly(allylamine hydrochloride)/poly(sodium styrenesulfonate) polyelectrolyte coating significantly inhibits the vaterite → calcite recrystallization (from hours to days) most likely due to suppression of the ion exchange giving an option to easily tune the release kinetics for a wide time scale, for example, for prolonged release. Moreover, the recrystallization of the coated crystals results in formulation of multilayer capsules keeping the feature of external manipulation. This study can help to design multifunctional microstructures with tailor-made characteristics for loading and controlled release as well as for external manipulation.

Hollow silver alginate microspheres for drug delivery and surface enhanced Raman scattering detection

Multifunctional silver alginate hydrogel microspheres are assembled via a template assisted approach using calcium carbonate cores. Sodium alginate is immobilized into the highly porous structure of calcium carbonate microspheres followed by cross-linking in the presence of silver ions. The simultaneous processes of the growth of silver nanoparticles in the alginate matrix and the removal of the calcium carbonate template are triggered by ascorbic acid. The abundance of silver nanoparticles and their interparticular junctions in the alginate network allow for the detection of solutes using Raman spectroscopy using the surface of the plasmonic microspheres. Rhodamine B was used to illustrate the potential applications of such multifunctional plasmonic alginate hydrogel microspheres for sensing at low concentrations. A proof of principle for using such particles for the quick identification of microorganisms is then demonstrated using the Escherichia coli bacterium.