Perspectives of growth of economic security by clustering of small innovation enterprises

The authors analyze the notion, sense, criteria, and indicators of evaluation of economic security and perform the evaluation of economic security of modern economic systems with the help of the offered methodology, which leads to the conclusion that one of the most successful countries are characterized by low level of economic security; therefore, there is a necessity for the search for perspectives of the increase of economic security. As a tool for increasing economic security, clustering is offered. The authors performed the structural analysis of formation of modern clusters and allowed allocating the problems of clustering which can be solved by clustering of small innovational enterprises. It is necessary that small innovational enterprises participate in the development of the program; their joint projects should at least concern, or, even better, solve their common problems (which will increase the competitiveness of cluster, as small innovational enterprises are connected by chains of value added with the same large companies); small innovational enterprises should participate – within the limits of their competencies – in the formation of the program of cluster development; there should be no artificial disunion between clusters of large enterprises and clusters of small innovational enterprises (which requires creation of common list of clusters). As a result of the research, the authors come to the conclusion that cluster is a form of increasing competitiveness within one country and in the global market, which stipulates the growth of national economic security. The highest efficiency of cluster is achieved by clustering small innovational enterprises, which stipulates the optimal level of competition in a cluster and leads to creation of innovations – which is a moving force of development of modern economy and the basis for economic security.peer-reviewe

Synergetic Enhancement of Tumor Double-Targeted MRI Nano-Probe

The conventional targeted delivery of chemotherapeutic and diagnostic agents utilizing nanocarriers is a promising approach for cancer theranostics. Unfortunately, this approach often faces hindered tumor access that decreases the therapeutic index and limits the further clinical translation of a developing drug. Here, we demonstrated a strategy of simultaneously double-targeting the drug to two distinct cites of tumor tissue: the tumor endothelium and cell surface receptors. We used fourth-generation polyamideamine dendrimers modified with a chelated Gd and functionalized with selectin ligand and alpha-fetoprotein receptor-binding peptide. According to the proposed strategy, IELLQAR peptide promotes the conjugate recruitment to the tumor inflammatory microenvironment and enhances extravasation through the interaction of nanodevice with P- and E-selectins expressed by endothelial cells. The second target moiety—alpha-fetoprotein receptor-binding peptide—enhances drug internalization into cancer cells and the intratumoral retention of the conjugate. The final conjugate contained 18 chelated Gd ions per dendrimer, characterized with a 32 nm size and a negative surface charge of around 18 mV. In vitro contrasting properties were comparable with commercially available Gd-chelate: r1 relaxivity was 3.39 for Magnevist and 3.11 for conjugate; r2 relaxivity was 5.12 for Magnevist and 4.81 for conjugate. By utilizing this dual targeting strategy, we demonstrated the increment of intratumoral accumulation, and a remarkable enhancement of antitumor effect, resulting in high-level synergy compared to monotargeted conjugates. In summary, the proposed strategy utilizing tumor tissue double-targeting may contribute to an enhancement in drug and diagnostic accumulation in aggressive tumors

Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles

The selection of technological parameters for nanoparticle formulation represents a complicated development phase. Therefore, the statistical analysis based on Box–Behnken methodology is widely used to optimize technological processes, including poly(lactic-co-glycolic acid) nanoparticle formulation. In this study, we applied a two-level three-factor design to optimize the preparation of nanoparticles loaded with cobalt (CoTPP), manganese (MnClTPP), and nickel (NiTPP) metalloporphyrins (MeP). The resulting nanoparticles were examined by dynamic light scattering, X-ray diffraction, Fourier transform infrared spectroscopy, MTT test, and hemolytic activity assay. The optimized model of nanoparticle formulation was validated, and the obtained nanoparticles possessed a spherical shape and physicochemical characteristics enabling them to deliver MeP in cancer cells. In vitro hemolysis assay revealed high safety of the formulated MeP-loaded nanoparticles. The MeP release demonstrated a biphasic profile and release mechanism via Fick diffusion, according to release exponent values. Formulated MeP-loaded nanoparticles revealed significant antitumor activity and ability to generate reactive oxygen species. MnClTPP- and CoTPP-nanoparticles specifically accumulated in tissues, preventing wide tissue distribution caused by long-term circulation of the hydrophobic drug. Our results suggest that MnClTPP- and CoTPP-nanoparticles represent the greatest potential for utilization in in anticancer therapy due to their effectiveness and safety

Oxidative Damage Induced by Phototoxic Pheophorbide a 17-Diethylene Glycol Ester Encapsulated in PLGA Nanoparticles

Pheophorbide a 17-diethylene glycol ester (XL-8), is a promising high-active derivative of known photosensitizer chlorin e6 used in photodynamic therapy. However, high lipophilicity and poor tumor accumulation limit XL-8 therapeutic application. We developed a novel XL-8 loaded with poly(D,L-lactide-co-glycolide) nanoparticles using the single emulsion-solvent evaporation method. The nanoparticles possessed high XL-8 loading content (4.6%) and encapsulation efficiency (87.7%) and a small size (182 ± 19 nm), and negative surface charge (−22.2 ± 3.8 mV) contributed to a specific intracellular accumulation. Sustained biphasic XL-8 release from nanoparticles enhanced the photosensitizer photostability upon irradiation that could potentially reduce the quantity of the drug applied. Additionally, the encapsulation of XL-8 in the polymer matrix preserved phototoxic activity of the payload. The nanoparticles displayed enhanced cellular internalization. Flow cytometry and confocal laser-scanning microscopy studies revealed rapid XL-8 loaded nanoparticles distribution throughout the cell and initiation of DNA damage, glutathione depletion, and lipid peroxidation via reactive oxygen species formation. The novel nanoformulated XL-8 simultaneously revealed a significant phototoxicity accompanied with enhanced photostability, in contrast with traditional photosensitizers, and demonstrated a great potential for further in vivo studies

Biocompatibility and Antimicrobial Activity of Electrospun Fibrous Materials Based on PHB and Modified with Hemin

The effect of the hemin (Hmi) on the structure and properties of nanocomposite electrospun materials based on poly-3-hydroxybutyrate (PHB) is discussed in the article. The additive significantly affected the morphology of fibers allowed to produce more elastic material and provided high antimicrobial activity. The article considers also the impact of the hemin on the biocompatibility of the nonwoven material based on PHB and the prospects for wound healing

Expression of acid cleavable Asp-Pro linked multimeric AFP peptide in E. coli

Abstract Background Difficult to express peptides are usually produced by co-expression with fusion partners. In this case, a significant mass part of the recombinant product falls on the subsequently removed fusion partner. On the other hand, multimerization of peptides is known to improve its proteolytic stability in E. coli due to the inclusion of body formation, which is sequence specific. Thereby, the peptide itself may serve as a fusion partner and one may produce more than one mole of the desired product per mole of fusion protein. This paper proposes a method for multimeric production of a human alpha-fetoprotein fragment with optimized multimer design and processing. This fragment may further find its application in the cytotoxic drug delivery field or as an inhibitor of endogenous alpha-fetoprotein. Results Multimerization of the extended alpha-fetoprotein receptor-binding peptide improved its stability in E. coli, and pentamer was found to be the largest stable with the highest expression level. As high as 10 aspartate-proline bonds used to separate peptide repeats were easily hydrolyzed in optimized formic acid-based conditions with 100% multimer conversion. The major product was represented by unaltered functional alpha-fetoprotein fragment while most side-products were its formyl-Pro, formyl-Tyr, and formyl-Lys derivatives. Single-step semi-preparative RP-HPLC was enough to separate unaltered peptide from the hydrolysis mixture. Conclusions A recombinant peptide derived from human alpha-fetoprotein can be produced via multimerization with subsequent formic acid hydrolysis and RP-HPLC purification. The reported procedure is characterized by the lower reagent cost in comparison with enzymatic hydrolysis of peptide fusions and solid-phase synthesis. This method may be adopted for different peptide expression, especially with low amino and hydroxy side chain content

Structural Optimization of Platinum Drugs to Improve the Drug-Loading and Antitumor Efficacy of PLGA Nanoparticles

Currently, molecular dynamics simulation is being widely applied to predict drug–polymer interaction, and to optimize drug delivery systems. Our study describes a combination of in silico and in vitro approaches aimed at improvement in polymer-based nanoparticle design for cancer treatment. We applied the PASS service to predict the biological activity of novel carboplatin derivatives. Subsequent molecular dynamics simulations revealed the dependence between the drug–polymer binding energy along with encapsulation efficacy, drug release profile, and the derivatives’ chemical structure. We applied ICP-MS analysis, the MTT test, and hemolytic activity assay to evaluate drug loading, antitumor activity, and hemocompatibility of the formulated nanoparticles. The drug encapsulation efficacy varied from 0.2% to 1% and correlated with in silico modelling results. The PLGA nanoparticles revealed higher antitumor activity against A549 human non-small-cell lung carcinoma cells compared to non-encapsulated carboplatin derivatives with IC50 values of 1.40–23.20 µM and 7.32–79.30 µM, respectively; the similar cytotoxicity profiles were observed against H69 and MCF-7 cells. The nanoparticles efficiently induced apoptosis in A549 cells. Thus, nanoparticles loaded with novel carboplatin derivatives demonstrated high application potential for anticancer therapy due to their efficacy and high hemocompatibility. Our results demonstrated the combination of in silico and in vitro methods applicability for the optimization of encapsulation and antitumor efficacy in novel drug delivery systems design