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  • Open access
  • 35 Reads
Self-assembling nano- and microparticles of chitosan L- and D-aspartate: preparation, structure, and biological activity

Our comprehensive study of solutions of chitosan (CS) D-aminoglucan in L- and D-aspartic acid (AspA) revealed the effects of counterionic association (self-organization) with the transition of macromolecules to the ionomeric state and phase segregation of the polymer substance into chiral nano- and microparticles. Optimal conditions for stabilizing particle dispersions by functionalizing their surface with a polysiloxane shell have been developed (pharmacologically active silicon tetraglycerolate was used for the first time as a sol-gel precursor). The effect of the L- and D-enantiomer of AspA on the structure, size, shape, and zeta potential of nano(micro)particles was studied by IR spectroscopy, dynamic light scattering, and electron and optical microscopy. It was found that chiral particles of CS·L-AspА and CS·D-AspА are non-toxic, hemo- and biocompatible, and also exhibit high growth-stimulating activity for test plants with the best effect for homochiral D-glucan·D-AspА particles. Experiments in vitro and in vivo revealed that chiral CS·L-(D-)AspA nano(micro)particles are biomimetic of rhizospheric bacteria Pseudomonas aureofaciens and could function as an immunizing elicitor, a curing fungicide, and a protective pesticide.

The research was supported by Russian Science Foundation Grant No. 22-23-00320, https://rscf.ru/project/22-23-00320/

  • Open access
  • 16 Reads
Hydrogels and nanostructures formed from ciprofloxacin–peptide conjugates

Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic that possesses potent activity against both Gram-positive and Gram-negative bacteria and is used to treat many infections.1 Despite its widespread use, ciprofloxacin is associated with side effects, which might be reduced by improving its pharmacokinetic properties. The chemical structure of ciprofloxacin is the source of some of its limitations, which include: 1) Poor membrane permeability, due to lipophobicity caused by the presence of polar groups; 2) poor transportation and absorption, due to poor water solubility caused by the flat aromatic structure.

Previous methods for improving the pharmacokinetic properties of ciprofloxacin have involved the synthesis of conjugates.2,3 Issues related to poor membrane permeability, transportation and absorption of drugs can also be improved by employing nanocarriers and nanomaterials. Encapsulation within nanocarriers allows targeted drug delivery, and reduced side effects as lower doses of drug can be administered. Nanocarriers that can be used for this purpose include nanoparticles and hydrogels.4,5 Our research group is interested in supramolecular hydrogels as drug delivery systems. Short amphiphilic peptides are often able to form hydrogels through self-assembly.

This present work desribes the synthesis of a panel of ciprofloxacin–peptide conjugates with the aim of forming hydrogels and related nanostructures to be used for the ‘self-delivery’ of antibacterial compounds. We assessed their hydrogelation ability, antibacterial activity and pharmacokinetic properties. Analysis by TEM microscopy revealed spherical nanostructures. The conjugates were unable to form hydrogels alone, but were able to form strong hydrogels with unique properties as co-gels with other peptide hydrogelators. The ciprofloxacin–peptide conjugates retained antibacterial activity. The drug release profile of ciprofloxacin from within the co-gels was also studied.

1. https://www.nhs.uk/medicines/ciprofloxacin
2. ChemistrySelect, 2016, 6, 1132. https://doi.org/10.1002/slct.201600091
3. Medicinal Chemistry, 2010, 6, 51. http://dx.doi.org/10.2174/157340610791321442
4. Nanomaterials, 2021, 11, 704. https://doi.org/10.3390/nano11030704
5. Soft Matter, 2022, 18, 3955. https://doi.org/10.1039/D2SM00121G

  • Open access
  • 25 Reads
Exploring Optical Nonlinearities of Glass Nanocomposites Made of Bimetallic Nanoparticles and Mesogenic Metal Alkanoates

The unique properties of nanomaterials along with their suitability for photonics applications can be explored by dispersing nanodopants in a transparent glass matrix. As a rule, the creation of glass nanocomposites involves a synthesis of nanoparticles followed by their dispersion in a glass host. This laborious two-step process can be simplified if glass-forming liquid crystals are used as a nanoreactor and host matrix. In this paper, we discuss a successful realization of this approach using mesogenic metal alkanoates for the fabrication of unconventional glass nanocomposites containing metal and/or bimetallic nanoparticles. More specifically, metal (gold and silver) and bimetallic (silver-gold) nanoparticles are synthesized in the liquid crystal phase of a glass-forming cadmium octanoate. Upon cooling cadmium octanoate samples containing the synthesized nanoparticles easily vitrify resulting in the formation of glass nanocomposites. The produced glass nanocomposites exhibit a relatively strong (10-8 – 10-7 esu) nonlinear-optical response tested by means of a Z-scan technique and utilizing visible (532 nm) and near-infrared (1064 nm) nanosecond laser pulses. The evaluated values of the effective nonlinear absorption coefficients and nonlinear refractive indices of the studied samples depend on their composition and on the intensity of laser beams thus revealing the presence of several nonlinear-optical mechanisms acting simultaneously. Potential applications of the designed glass nanocomposites are also discussed.

  • Open access
  • 16 Reads
Decellularized extracellular matrix Polycaprolactone/Chitosan composite nanofibrous scaffolds for periodontal tissue engineering

Periodontitis is an inflammatory infection caused by bacterial plaque accumulation that affects the periodontal tissues supporting the teeth. Current treatments lack bioactive signals to induce tissue repair and coordinated regeneration of the periodontal tissues, thus alternative strategies are needed to improve clinical outcomes. Cell-derived extracellular matrix (ECM) has been used in combination with biomaterials to enhance their biofunctionality for various tissue engineering (TE) applications. In this work, bioactive cell-derived ECM loaded electrospun polycaprolactone/chitosan (PCL-CTS) nanofibrous scaffolds were developed using lyophilized decellularized ECM (dECM) derived from human Periodontal Ligament Stem Cells (hPDLSCs). This work's aims were to fabricate and characterize cell-derived ECM electrospun PCL-CTS scaffolds and assess their ability to enhance the osteogenic differentiation of hPDLSCs, envisaging periodontal TE applications. hPDLSCs were cultured and used for dECM production, aiming to recreate the periodontal niche. The physicochemical properties of electrospun scaffolds were assessed (structure, elemental composition, hydrophilicity, thermal and mechanical properties) and the effects of CTS and dECM presence on the scaffolds' properties were determined. PCL-CTS and PCL-CTS-ECM scaffolds were composed of homogeneous beadless nanofibers. Osteogenic differentiation of hPDLSCs was performed on PCL, PCL-CTS and PCL-CTS-ECM electrospun scaffolds for 21 days. The obtained results demonstrate that PCL-CTS-ECM scaffolds significantly enhanced cell proliferation compared to PCL and PCL-CTS scaffolds, while maintaining similar physical and mechanical properties of PCL-CTS scaffolds. PCL-CTS scaffolds showed higher levels of calcium deposition and cell mineralization than PCL scaffolds. PCL-CTS-ECM scaffolds enhanced the osteogenic differentiation of hPDLSCs as confirmed by increased alkaline phosphatase (ALP) activity, calcium deposition and upregulation of osteogenic marker-genes. Overall, our results show that ECM loaded electrospun nanofibrous scaffolds enhanced the proliferation and osteogenic differentiation of hPDLSCs. Notably, this work describes the first use of lyophilized cell-derived ECM loaded electrospun scaffolds for periodontal TE applications and highlights its potential as a promising therapeutic strategy for periodontitis.

  • Open access
  • 17 Reads
Microemulsions in the systems with lecithin and oils from tropical plants for drug delivery

Microemulsions are thermodynamically stable dispersions of oil and water containing nanometer-sized droplets stabilized by a surfactant. Microemulsions containing biocompatible surfactants, such as lecithin, are promising carriers for drug delivery. It has been shown that oil from the tropical plant gac (Momordica cochinchinensis) and turmeric essential oil can be used to obtain reverse microemulsions in the systems lecithin - oleic acid - vaseline oil - vegetable oil - essential oil - water. At least 6.5 wt.% of water can be introduced into the microemulsion at a lecithin concentration in the organic phase of 20 wt.%, a ratio of vaseline oil and gac oil 1:1 by weight and a molar ratio of oleic acid and lecithin from 0.2 to 0.8. Depending on the concentration of water and lecithin, the hydrodynamic diameter of microemulsion droplets varies in the range from 3 to 21 nm; a linear dependence of the diameter on W is shown. Both after heating to 60 ºС and cooling, and after freezing at -20 ºС and subsequent thawing, the structure of the microemulsion was restored, the droplet size practically did not change. Using IR-Fourier spectroscopy, it was shown that for the microemulsion with the molar ratio of water and lecithin W=14, the fraction of bulk (free) water in the droplets was 36.5 mol %, the fraction of hydration water (bound to polar groups of surfactants) was 55.0 mol %, the fraction of water trapped between hydrocarbon chains – 8.5 mol.%. The resulting reverse microemulsions are characterized by a low rate of release of water-soluble substances: in 6 hours, approximately 3,2% of the dye Rhodamine C was released, which allows the development of drugs with a sustained release of medicinal substances.

  • Open access
  • 23 Reads
PCL NANOMODIFIED COATING FOR THE PROTECTION OF THERMOCHROMIC PRINTS ON PACKAGING

In graphic industry, thermochromic inks are used primarily in development of "smart" packaging for different applications, such as indicators of the product's current temperature or an out-of-boundary temperature reading. Thermochromic inks change their colouration with the change of temperature. During storage and transportations of products, as well as during their use, the packaging may come into contact with various chemicals, which may bring into question the chemical stability and therefore the functionality of thermochromic sensor. Polycaprolactone (PCL) is a biodegradable polymer which can find usage in various applications due to its good characteristics. The aim of this work was to determine the effect of a coating made of the biodegradable PCL polymer, and a PCL coating with the addition of zinc oxide or titanium dioxide, on the chemical stability and colorimetric properties of an offset thermochromic ink based on leuco dyes. For this purpose, full-tone prints of thermochromic ink were made on the printing substrate, appropriate coatings were applied to them, and the resulting samples were tested for chemical stability to water, soap, and ethanol according to ISO 2836:2021 standard. The results show that the coatings have no significant negative impact on the colorimetric values of the prints compared to uncoated prints, and the chemical stability of the thermochromic prints is significantly improved in the case of exposure to ethanol, especially a strong, 96% ethanol solution.

  • Open access
  • 17 Reads
Synthesis and characterization of a bifunctional platform based on magnetite-gold nanoparticles for theranostics of cancer

One of the most interesting objects in terms of use in biomedicine are the hybrid structures based on magnetic nanoparticles (NPs) and NPs of noble metals which make it possible to simultaneously introduce two types of ligands onto the surface of NPs for their further use for photodynamic cancer therapy (PDT) (a combination of a photosensitizer (PS) for therapy and a fluorophore (FP) for platform detection). Synthesis and the research NPs Fe3O4-Au with "dumbell" structure as the bifunctional platform for therapy of oncological diseases was the purpose of this work. As a result of iron pentacarbonyl decomposition in diphenyl ethers in the presence of tetrachlorurates of hydrogen hybrid NPs of magnetite and gold with a size of Fe3O4 10,8 ± 1.5 nanometers and Au 4.4 ± 0.8 nanometers (according to the TEM) stabilized by oleic acid are synthesized. By results of the X-ray phase analysis the synthesized NPs have crystal structure like "spinel" with the period of a lattice of 0.8387 nanometers. By results of measurement of the NPs magnetic properties had magnetization of saturation of 62 Am2 · kg (Fe3O4)-1 and coercive force 13 E. NPs modified 3.4-dihydroxyphenylacetic acid (DOPAC) for the subsequent covering the stabilizing polyethyleneglycol (PEG) by a carbodiimide method. As in one system it is necessary to unite two different substances (PS and FP), as "link" Fe3O4-Au NPs (stabilized) were used. When studying the optical properties of the synthesized platform Fe3O4-Au/PS/FP, the emission and absorption peaks of PS and FP were identical to the peaks of PS and FP in solution. Also analyses of NMR and IR spectroscopy confirmed structure of a system. Further is going to calculate physical and chemical parameters of the synthesized system for optimization and therapy of in vitro and in vivo.

  • Open access
  • 33 Reads
Plug-and-Play Lymph Node-on-Chip: Possibility of Passage of Polymer Capsules to Secondary Tumor, Designed By Combination Of Cell Spheroid, Collagen Sponge and T-cells

Towards the improvement of the efficient study of drugs and contrast agents, the 3D microfluidic platforms are currently being actively developed for testing these substances and particles in vitro. Such bioengineering solutions, can bring the system much closer to real-world conditions without the unnecessary use of laboratory animals. Also, the application of engineering methods allows the fine-tuning of the resulting structures for their installation and long-term observation in imaging systems. We have elaborated a microfluidic lymph node-on-chip (LNOC) as a tissue engineered model of a secondary tumor in lymph node (LN) formed due to the metastasis process. The developed chip has a collagen sponge with a 3D spheroid of 4T1 cells located inside, simulating secondary tumor in the lymphoid tissue. This collagen sponge has a morphology and porosity comparable to that of a native human LN. To demonstrate the suitability of the obtained chip for pharmacological appli-cations, we used it to evaluate the effect of contrast agent/drug carrier size, on the penetration and accumulation of particles in 3D spheroids modeling secondary tumor. For this, the 0.3, 0.5 and 4 μm bovine serum albumin (BSA)/tannic acid (TA) capsules were mixed with lymphocytes and pumped through the developed chip.
Thus, in our study, 0.3 μm capsules, which penetrated well into the spheroid, turned out to be the most effective for delivery. These results highlight the potential of our LNOC for use in particle and contrast agent testing. They also demonstrate that the LNOC is an attractive alternative for further analysis and understanding of the effectiveness of developed drug delivery vehicles and contrast agents delivered to cells and organs. Moreover, some findings that we have obtained during the development of our device can be used for the elab-oration of other types of lab-on-chip systems.

  • Open access
  • 13 Reads
Study of photoresistor fabrication based on mercury chalcogenides applying various ligand exchanges

Colloidal quantum dots (CQDs) of mercury telluride have attracted a lot of attention in the last decade because of their unique properties. Mercury telluride-based CQDs are promising candidates for use in various fields of engineering and science, due to the incomparable combination of the large radius of the Boron exciton (30 nm) and the band gap (0 eV) for bulk material. This ensures the spectral rearrangement of the properties of the CQDs from the near to far IR range. On the basis of this material the photodetectors, lasers and telecommunication devices are being under active development. Mercury sulfide CQDs are a material that has been little investigated, and based on our research, interesting results have been obtained.

Photosensitive thin films are created from sols of coloidal quantum dots of mercury chalcogenides for the use in photodevices. The ligand exchange procedure strongly affects the photoelectric properties of thin films, but it has an additional impact on their properties.

In order to optimize the fabrication of photoresistors the several additional aspects were studied like morphology and thicknesses of created films. HgTe and HgS CQDs were applied on glass substrates and interdigitated electrodes by dip-coating and spin-coating methods applying layer-by-layer deposition technique. The surface morphology and roughness of the obtained films were studied using atomic force microscope. Film thicknesses were also determined depending on various ligand exchange (ethandithiol, sulfide, thiocyanate, iodide). Photosensitive films were created by applying layers of colloidal quantum dots of mercury chalcogenides to golden electrodes and their volt-ampere characteristics were determined.

As part of the work, measurements were made of both - dark volt-ampere characteristics (VAC) and light VAC when illuminated with a laser at 980 nm, for thin films of mercury chalcogenides. After replacing the original shells with I-, S2-, SCN- and ethandithiol-1,2, the results obtained were analyzed.

  • Open access
  • 22 Reads
pMyc and pMax Peptides Nanosystems for a Prostate Cancer Treatment, In Vitro Assays

The Myc transcription factor and its associated Max protein have an essential role in developing several types of cancers, including prostate cancer. They act through the dimerization into a Myc-Max heterodimer and the binding to specific DNA sequences known as enhancer box (E-box). Disrupting the Myc- Max heterodimer interaction or its binding to canonical E-box sequences (CME) to disrupt gene transcription is a promising strategy to treat cancer. Using computational biology tools, we designed pMyc and pMax peptides from Myc and Max reference sequences and evaluated their ability to bind specifically CME through an electrophoretic mobility shift assay (EMSA). We then coupled them to AuNPs and evaluated the hemocompatibility and the cytotoxic effect in three different prostate adenocarcinoma cell lines (LNCaP, PC-3, and DU145) and a non-cancerous cell line (Vero CCL-81). The EMSA results suggest that the pMyc-pMax dimers bind to CMEs. Through UV-Vis absorption spectra, we determined peptide conjugation to the AuNPs. The hemolysis test showed little hemolytic activity for the nanosystems (NS) at the concentrations (5, 0.5, and 0.05 ng/ µL) evaluated. Cell viability assays showed mixed results depending on which cell line was being evaluated. Overall, results suggest that NS with pMyc and pMax peptides might be suitable for further research regarding Myc-driven prostate adenocarcinomas.

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