Maria N. Antipina

Remote control over guidance and release properties of composite polyelectrolyte based capsules

Polyelectrolyte multilayer capsules represent a unique tool to fabricate micron- and submicron-sized delivery systems with the properties of external guidance by means of remote physical influence. Embedding of nanoparticles into polyelectrolyte multilayer constructs opens up the opportunities to navigate the capsules with magnetic field and in-situ trigger the release of encapsulated material in response to the physical stimuli, such as light and ultrasound. So far, optically- and magnetically-induced addressing of the polyelectrolyte multilayer capsules internalized by the living cells in-vitro has been demonstrated. In this review, we discuss the state of the art, future perspectives and anticipated obstacles of in-vivo and in-vitro applications of the polyelectrolyte capsules performing remotely controlled release delivery of bioactives.

CaCO3 vaterite microparticles for biomedical and personal care applications

Among the polymorph modifications of calcium carbonate, the metastable vaterite is the most practically important. Vaterite particles are applied in regenerative medicine, drug delivery and a broad range of personal care products. This manuscript scopes to review the mechanism of the calcium carbonate crystal growth highlighting the factors stabilizing the vaterite polymorph in the most cost efficient synthesis routine. The size of vaterite particles is a crucial parameter for practical applications. The options for tuning the particle size are also discussed.

Layer-by-layer assembled multilayer shells for encapsulation and release of fragrance.

Layer-by-layer assembled shells are prospective candidates for encapsulation, stabilization, storage, and release of fragrances. A shell comprising four alternative layers of a protein and a polyphenol is employed to encapsulate the dispersed phase of a fragrance-containing oil-in-water emulsion. The model fragrance used in this work consists of 10 ingredients, covering a range of typically employed aroma molecules, all premixed in equal mass and with sunflower oil acting as the base. The encapsulated emulsion is stable after 2 months of storage at 4 °C as revealed by static light scattering and confocal laser scanning microscopy. Gas chromatography/mass spectrometry data show that the encapsulation efficiency of 8 out of 10 fragrance ingredients depends on the water solubility: the less water-soluble an ingredient, the more of it is encapsulated. The amount of these fragrance ingredients remaining encapsulated decreases linearly upon emulsion incubation at 40 °C and the multilayer shell does not hinder their release. The other two fragrance ingredients having the lowest saturation vapor pressure demonstrate sustained release over 5 days of incubation at 40 °C. The composition of released fragrance remains almost constant over 3 days of incubation, upon further incubation it becomes enriched with these two ingredients when others start to be depleted.

Multilayer Capsules of Bovine Serum Albumin and Tannic Acid for Controlled Release by Enzymatic Degradation

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.

Encapsulation of basic fibroblast growth factor by polyelectrolyte multilayer microcapsules and its controlled release for enhancing cell proliferation.

Basic fibroblast growth factor (FGF2) is an important protein for cellular activity and highly vulnerable to environmental conditions. FGF2 protected by heparin and bovine serum albumin was loaded into the microcapsules by a coprecipitation-based layer-by-layer encapsulation method. Low cytotoxic and biodegradable polyelectrolytes dextran sulfate and poly-L-arginine were used for capsule shell assembly. The shell thickness-dependent encapsulation efficiency was measured by enzyme-linked immunosorbent assay. A maximum encapsulation efficiency of 42% could be achieved by microcapsules with a shell thickness of 14 layers. The effects of microcapsule concentration and shell thickness on cytotoxicity, FGF2 release kinetics, and L929 cell proliferation were evaluated in vitro. The advantage of using microcapsules as the carrier for FGF2 controlled release for enhancing L929 cell proliferation was analyzed.

Individually Addressable Patterned Multilayer Microchambers for Site-Specific Release-On-Demand

Patterned arrays of light-responsive microchambers are suggested as candidates for site-specific release of chemicals in small and precisely defined quantities on demand. A composite film is made of poly(allylammonium)-poly(styrene sulfonate) multilayers and gold nanoparticles incorporated between subsequent stacks of polyelectrolytes. The film shaped as microchambers is loaded with colloid particles or oil-soluble molecules. The microchambers are sealed onto a glass slide precoated with an adhesive poly(diallyldimethylammonium)-poly(styrene sulfonate) multilayer film. A focused laser beam is used for remote addressing the individual microchambers and site-specific release of the loaded cargo.

Emulsion-based techniques for encapsulation in biomedicine, food and personal care

The manuscript scopes to review the emulsion-based techniques aimed for encapsulation of active compounds found in biomedical applications, functional foodstuff, skin care and cosmetology. The advantages, limitations and outlook are discussed for each method.

Micropackaging via layer-by-layer assembly: microcapsules and microchamber arrays

Abstract The micropackaging of chemical compounds in a small and precisely defined quantity, which can be encased, stored, is essential for response to a specific chemical, biological or physical trigger in a controllable manner is one of the premier challenges in the development of delivery systems. In this review, the authors discuss the application of layer-by-layer (LbL) assemblies of macromolecules for micropackaging and controlled release of various types of cargo. The LbL assembly method provides unique opportunities by incorporation of different functional and responsive layer constituents tailored into one entity. Micron and submicron sized capsules made on colloidal templates are used for biomolecule encapsulation and enable time- and site-specific release when triggered by pH, temperature, specific enzymes, mechanic load, light, ultrasound, or magnetic field. In comparison to individual capsules, the authors discuss the recently introduced micropackaging approach involving cargo loading into arrays of microchambers, made by a combination of imprinting technology and LbL assembly. In conclusion, the authors summarise advantages and fabrication obstacles for micropackaging in capsules and microchambers and discuss already existing as well as potential future applications.

Patterned microcontainers as novel functional elements for µTAS and LOC

Using nanoimprint lithography, arrays of highly ordered patterns of polyelectrolyte multilayer microcapsules consisting of alternating layers of poly(allylamine hydrochloride) and poly(sodium 4-styrene sulfonate) have been achieved. Anchoring the capsules on a pre-patterned substrate facilitates the utilization of their various capabilities in lab-on-a chip devices. In this paper we have demonstrated a very effective method to entrap soft capsules into surface cavities. Supported microcapsules were applied as the depots for loading and storage of macromolecular cargo (glucose oxidase and peroxidase) and as preserved microvessels for the cascade of enzymatic reactions. The loading of capsules was achieved under a pre-determined pH environment. This development is potentially useful for the realization of novel multianalytical systems for catalytic, bio-affinity and pH detection with protected sensing molecules.

Layered polymeric capsules inhibiting the activity of RNases for intracellular delivery of messenger RNA

Intracellular delivery of messenger RNA (mRNA) is a promising approach for experimental and therapeutic manipulation of cellular activity. However, environmental RNase hinders reliable handling of mRNA for experimental and therapeutic use. In this study, biodegradable capsules composed of dextran sulfate and poly-l-arginine in the layer-by-layer (LbL) fashion are employed for the protection and delivery of mRNA. Our results demonstrate that addition of RNase inhibitors to mRNA while co-precipitation with CaCO3 and subsequent LbL encapsulation are both crucial to preserve the integrity of mRNA. The expression of functional luciferase enzyme in HEK293T human embryonic kidney cells after incubation with synthetic luciferase-encoding mRNA capsules indicates the reliability of the encapsulating system and cellular intake of functional mRNAs. These improvements in mRNA encapsulation should provide essential basis for microcapsule-based mRNA delivery for further applications.