With the purpose to replace expensive and significantly cytotoxic positively charged polypeptides in biodegradable capsules formed via Layer-by-Layer (LbL) assembly, multilayers of bovine serum albumin (BSA) and tannic acid (TA) are obtained and employed for encapsulation and release of model drugs with different solubility in water: hydrophilic-tetramethylrhodamine-isothiocyanate-labeled BSA (TRITC-BSA) and hydrophobic 3,4,9,10-tetra-(hectoxy-carbonyl)-perylene (THCP). Hydrogen bonding is proposed to be predominant within thus formed BSA/TA films. The TRITC-BSA-loaded capsules comprising 6 bilayers of the protein and polyphenol are benchmarked against the shells composed of dextran sulfate (DS) and poly-l-arginine (PARG) on degradability by two proteolytic enzymes with different cleavage site specificity (i.e., α-chymotrypsin and trypsin) and toxicity for murine RAW264.7 macrophage cells. Capsules of both types possess low cytotoxicity taken at concentrations equal or below 50 capsules per cell, and evident susceptibility to α-chymotrypsin resulted in release of TRITC-BSA. While the BSA/TA-based capsules clearly display resistance to treatment with trypsin, the assemblies of DS/PARG extensively degrade. Successful encapsulation of THCP in the TRITC-BSA/TA/BSA multilayer is confirmed, and the release of the model drug is observed in response to treatment with α-chymotrypsin. The thickness, surface morphology, and enzyme-catalyzed degradation process of the BSA/TA-based films are investigated on a planar multilayer comprising 40 bilayers of the protein and polyphenol deposited on a silicon wafer. The developed BSA/TA-based capsules with a protease-specific degradation mechanism are proposed to find applications in personal care, pharmacology, and the development of drug delivery systems including those intravenous injectable and having site-specific release capability.

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Incorporation of locally produced signaling molecules into cell-derived vesicles may serve as an endogenous mediator delivery system. We recently reported that levels alpha-2-macroglobulin (A2MG)-containing microparticles are elevated in plasma from patients with sepsis. Herein, we investigated the immunomodulatory actions of A2MG containing microparticles during sepsis. Administration of A2MG-enriched (A2MG-E)-microparticles to mice with microbial sepsis protected against hypothermia, reduced bacterial titers, elevated immunoresolvent lipid mediator levels in inflammatory exudates and reduced systemic inflammation. A2MG-E microparticles also enhanced survival in murine sepsis, an action lost in mice transfected with siRNA for LRP1, a putative A2MG receptor. In vitro, A2MG was functionally transferred onto endothelial cell plasma membranes from microparticles, augmenting neutrophil–endothelial adhesion. A2MG also modulated human leukocyte responses: enhanced bacterial phagocytosis, reactive oxygen species production, cathelicidin release, prevented endotoxin induced CXCR2 downregulation and preserved neutrophil chemotaxis in the presence of LPS. A significant association was also found between elevated plasma levels of A2MG-containing microparticles and survival in human sepsis patients. Taken together, these results identify A2MG enrichment in microparticles as an important host protective mechanism in sepsis.

Nanocomposite microcapsules with both gold and magnetite nanoparticles in the shell were prepared in a layer-by-layer procedure using biocompatible polyelectrolytes and nanoparticles. The process of a nanocomposite multilayer formation was investigated using a quartz crystal microbalance (QCM). In addition, nanocomposite microcapsules were characterized by atomic force microscopy (AFM), transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDX). It is found that the amount of adsorbed nanoparticles is similar for nanoparticles of various sizes, while the concentration of gold nanoparticles in the shell is higher for smaller nanoparticles. Adsorption of gold nanoparticles is found to be more effective than adsorption of magnetic nanoparticles. Multifunctionality of microcapsules is manifested by dual: magnetic and optical responses. Iron oxide nanoparticles embedded in the microcapsule shell allowed for control over capsules positioning by external magnetic fields. Furthermore, the nanocomposite microcapsules could be opened by laser irradiation; these results are of interest for medical and biological applications.

The possibility of protein release from polymeric microcapsules by means of low-power (up to a maximum of 3.2 W) high-frequency (850 kHz) ultrasound was studied. The release efficiency using these ultrasonic parameters that are close to those currently used in medical diagnostic and ultrasound treatment was compared to that achieved with a conventional 20 kHz 70 W ultrasonic probe. Microcapsules were made by polyelectrolyte multilayer assembly on 3-5 mm calcium carbonate particles with co-precipitated fluorescently labelled protein. Ultrasound induced protein release was monitored by supernatant fluorescence increase after sonication. The release efficiency is improved by the presence of gold nanoparticles in the microcapsule shell. The amount of gold nanoparticles in the shell was found to play an important role in release efficiency. The irradiation was carried out at several intensities and exposure times and evidence of microcapsule rupture after treatment was obtained by confocal and scanning electron microscopy.

Single‐wall carbon nanotubes modified by anionic polyelectrolyte molecules are embedded into the shells of microcapsules. Carbon nanotubes serve as rigid rods in a softer polymeric capsule, which forms a free‐standing shell upon treatment with glutaraldehyde and subsequent drying. The embedded carbon nanotubes exhibit a broad absorption in the UV–near‐infrared part of the spectrum, and that allows point‐wise activation and opening of the microcapsules by laser. Raman signal analysis shows changes of carbon‐nanotube‐specific lines after high‐power laser irradiation, which is characteristic of the formation of disordered carbonlike structures. These polyelectrolyte/carbon nanotube composite capsules represent a novel light‐addressable type of microcontainers.

The elaboration of biocompatible and biodegradable carriers for photosensitizer targeted delivery is one of the most promising approaches in a modern photodynamic therapy (PDT). This approach is aimed at reducing sides effects connected with incidental toxicity in healthy tissue whilst also enhancing drug accumulation in the tumour area. In the present work, Photosens-loaded calcium carbonate (CaCO3) submicron particles in vaterite modification are proposed as a novel platform for anticancer PDT. Fast penetration of the carriers (0.9±0.2μm in diameter) containing 0.12% (w/w) of the photosensitizer into NIH3T3/EGFP cells is demonstrated. The captured particles provide the dye localization inside the cell increasing its local concentration, compared with "free" Photosens solution which is uniformly distributed throughout the cell. The effect of photosensitizer encapsulation into vaterite submicron particles on cell viability under laser irradiation (670nm, 19mW/cm(2), 10min) is discussed in the work. As determined by a viability assay, the encapsulation renders Photosens more phototoxic. By this means, CaCO3 carriers allow improvement of the photosensitizer effectiveness supposing, therefore, the reduction of therapeutic dose. Summation of these effects with the simplicity, upscalability and cheapness of fabrication, biocompatibility and high payload ability of the vaterite particles hold out the prospect of a novel PDT platform.

The concept of enzyme-assisted substrate sensing based on use of fluorescent markers to detect the products of enzymatic reaction has been investigated by fabrication of micron-scale polyelectrolyte capsules containing enzymes and dyes in one entity. Microcapsules approximately 5 μm in size entrap glucose oxidase or lactate oxidase, with peroxidase, together with the corresponding markers Tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) dichloride (Ru(dpp)) complex and dihydrorhodamine 123 (DHR123), which are sensitive to oxygen and hydrogen peroxide, respectively. These capsules are produced by co-precipitation of calcium carbonate particles with the enzyme followed by layer-by-layer assembly of polyelectrolytes over the surface of the particles and incorporation of the dye in the capsule interior or in the multilayer shell. After dissolution of the calcium carbonate the enzymes and dyes remain in the multilayer capsules. In this study we produced enzyme-containing microcapsules sensitive to glucose and lactate. Calibration curves based on fluorescence intensity of Ru(dpp) and DHR123 were linearly dependent on substrate concentration, enabling reliable sensing in the millimolar range. The main advantages of using these capsules with optical recording is the possibility of building single capsule-based sensors. The response from individual capsules was observed by confocal microscopy as increasing fluorescence intensity of the capsule on addition of lactate at millimolar concentrations. Because internalization of the micron-sized multi-component capsules was feasible, they could be further optimized for in-situ intracellular sensing and metabolite monitoring on the basis of fluorescence reporting.