The applicability of beam-plasma chemical reactors generating cold hybrid plasma for the production of noncytotoxic polymeric surfaces with high hydrophilicity and good biocompatibility with human fibroblast culture and human red blood cells was studied. Oxygen hybrid plasma was excited by the joint action of a continuous scanning electron beam and a capacity-coupled RF-gas discharge. Experiments showed that hybrid plasma treatment caused polar oxygen-containing functional group formation in the surface layer of poly (ethylene terephthalate) films. No thermal or radiative damage in tested polymer samples was found. The plasma-modified polymers turned out to be noncytotoxic and revealed good biocompatibility with human fibroblasts BJ-5ta as well as lower hemolytic activity than untreated poly (ethylene terephthalate). Experiments also demonstrated that no phenomena caused by the electrostatic charging of polymers occur in hybrid plasma because the electron beam component of hybrid plasma eliminates the item charge when it is treated. The electron beam can effectively control the reaction volume geometry as well as the fluxes of active plasma particles falling on the item surface. This provides new approaches to the production of abruptly structured patterns or smooth gradients of functionalities on a plane and 3D polymeric items of complicated geometry.

The Maillard-type WPI-chitosan conjugate was prepared through dry heating at 60°C and 75% relative humidity for 72 hours at a weight excess of WPI (8.7-fold) relative to CHIT (75% of deacetylation). The focus of the study was the soluble fraction (68% w/w) of the WPI-CHIT conjugate in the pI range of WPI (pH 4.5). SDS-PAGE analysis revealed that 16% of the total WPI was covalently bonded to CHIT. SDS-PAGE and SEC identified a 29% degree of binding for α-lactalbumin. DSC, fluorimetry, and FTIR detected unfolding of globular whey proteins in the conjugate. The conjugate encapsulated 94% of phosphatidylcholine liposomes loaded with fish oil and curcumin, resulting in complex particles. EPRS, DSC, fluorimetry, laser light scattering, tensiometry, and TEM provided insights into the structural and thermodynamic parameters underlying the functionality of the latter: water solubility, protective ability for encapsulated nutraceuticals, and lower foaming ability compared to that of the WPI-CHIT conjugate.

Electrospun biomimetic materials based on polyester of natural origin poly-3-hudroxybutyrate (PHB) modified with hemin (Hmi) and fibrinogen (Fbg) represent a great interest and are potentially applicable in various fields. Here, we describe formulation of the new fibrous PHB-Fbg and PHB-Hmi-Fbg materials with complex structure for biomedical application. The average diameter of the fibers was 3.5 μm and 1.8 μm respectively. Hmi presence increased porosity from 80 % to 94 %, significantly reduced the number of defects, ensured the formation of a larger number of open pores, and improved mechanical properties. Hmi presence significantly improved the molding properties of the material. Hmi facilitated effective Fbg adsorption on the of the PHB wound-healing material, ensuring uniform localization of the protein on the surface of the fibers. Next, we evaluated cytocompatibility, cell behavior, and open wound healing in mice. The results demonstrated that PHB-Fbg and PHB-Hmi-Fbg electrospun materials had pronounced properties and may be promising for early-stage wound healing - the PHB-Hmi-Fbg sample accelerated wound closure by 35 % on the 3rd day, and PHB-Hmi showed 45 % more effective wound closure on the 15th day.

Metal-organic frameworks (MOFs) are widely used in the biomedical industry. In this study, we developed a new method for obtaining a metal-organic structure of strontium and terephthalic acid, Sr(BDC), and an alternative activation method for removing DMF from the pores. Sr(BDC) MOFs were successfully prepared and characterized by XRD, FTIR, TGA, and SEM. The importance of the activation steps was confirmed by TGA, which showed that the Sr(BDC)(DMF) sample can contain up to a quarter of the solvent (DMF) before activation. In our study, IR spectroscopy confirmed the possibility of removing DMF by ethanol treatment from the Sr-BDC crystals. A comparative analysis of the effect of the activation method on the specific surface and pore size of Sr-BDC and its sorption properties using the model drug doxorubicin showed that due to the undeveloped surface of the Sr-(BDC)(DMF) sample, it is not possible to obtain an adsorption isotherm and determine the pore size distribution, thus showing the importance of the activation step. Cytotoxicity and apoptosis assays were carried out to study the biological activity of MOFs, and we observed relatively low toxicity in the tested concentration range after 48 h, with over 92% cell survival for Sr(BDC)(DMF) and Sr(BDC)(260 °C), with a decrease only in the highest concentration (800 mg L-1). Similar results were observed in our apoptosis assays, as they revealed low apoptotic population generation of 2.52%, 3.23%, and 2.77% for Sr(BDC)(DMF), Sr(BDC) and Sr(BDC)(260 °C), respectively. Overall, the findings indicate that ethanol-activated Sr(BDC) shows potential as a safe and effective material for drug delivery.

In this study, we described physico-chemical properties of novel nanoformulation of photosensitizer-pyropheophorbide α 17-diethylene glycol ester (XL) (chlorophyll α derivative), revealing insights into antitumor activity and maintaining quality, meeting the pharmaceutical approach of new nanoformulation design. Our formulation, based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles, increased XL solubility and selective tumor-targeted accumulation. In our research, we revealed, for the first time, that XL binding to polyvinyl alcohol (PVA) enhances XL photophysical activity, providing the rationale for PVA application as a stabilizer for nanoformulations. Results of FTIR, DSC, and XRD revealed the physical interactions between XL and excipients, including PVA, indicating that the encapsulation maintained XL binding to PVA. The encapsulated XL exhibited higher photophysical activity compared to non-encapsulated substance, which can be attributed to the influence of residual PVA. Gamma-irradiation led to degradation of XL; however, successful sterilization of the samples was achieved through the filtration. Importantly, the encapsulated and sterilized XL retained cytotoxicity against both 2D and 3D tumor cell models, demonstrating the potential of the formulated NP–XL for photodynamic therapy applications, but lacked the ability to reactivate epigenetically silenced genes. These findings provide valuable insights into the design and characterization of PLGA-based nanoparticles for the encapsulation of photosensitizers.

Unsaturated fatty acids, such as oleic acid (OA) and linoleic acid (LA), are promising antimicrobial and cytostatic agents. We modified OA and LA with thymol (TOA and TLA, respectively) to expand their bioavailability, stability, and possible applications, and encapsulated these derivatives in polymeric nanoparticles (TOA-NPs and TLA-NPs, respectively). Prior to synthesis, we performed mathematical simulations with PASS and ADMETlab 2.0 to predict the biological activity and pharmacokinetics of TOA and TLA. TOA and TLA were synthesized via esterification in the presence of catalysts. Next, we formulated nanoparticles using the single-emulsion solvent evaporation technique. We applied dynamic light scattering, Uv-vis spectroscopy, release studies under gastrointestinal (pH 1.2–6.8) and blood environment simulation conditions (pH 7.4), and in vitro biological activity testing to characterize the nanoparticles. PASS revealed that TOA and TLA have antimicrobial and anticancer therapeutic potential. ADMETlab 2.0 provided a rationale for TOA and TLA encapsulation. The nanoparticles had an average size of 212–227 nm, with a high encapsulation efficiency (71–93%), and released TOA and TLA in a gradual and prolonged mode. TLA-NPs possessed higher antibacterial activity against B. cereus and S. aureus and pronounced cytotoxic activity against MCF-7, K562, and A549 cell lines compared to TOA-NPs. Our findings expand the biomedical application of fatty acids and provide a basis for further in vivo evaluation of designed derivatives and formulations.

N-terminal amino acid sequences of structural proteins of three flaviviruses, yellow fever, St. Louis encephalitis, and dengue-2 viruses, have been obtained. The glycoproteins of these three viruses are 52–60% conserved in the region sequenced, depending upon which pair of viruses are compared, and 40% of the amino acids are invariant in all three viruses. Thus, flaviviruses are closely related and have in all probability descended from a common ancestor. Furthermore, residues important in the secondary structure of proteins are conserved, suggesting that the overall conformation of the glycoproteins is the same in all three viruses while considerable variation in the primary sequence can be accommodated. The N-terminal regions of the nucleocapsid proteins of yellow fever and St. Louis encephalitis viruses show markedly less homology (25%) and this region is highly basic with one-quarter (yellow fever) or one-third (St. Louis encephalitis) of the residues being lysine or arginine. N-terminal sequences for the M protein of yellow fever and for NV2(GP19) of St. Louis encephalitis viruses are also reported.

The combination of two or more medications is increasingly more common in the development of new treatment guidelines for common diseases. Thus, the use of combinations of histone deacetylase inhibitors with chemotherapeutic agents is a current trend in solid tumor treatment. The aim of this study was to investigate an effective vorinostat (SAHA) to doxorubicin (DOX) ratio for the treatment of different subtypes of breast cancer. The survival of HCC-1954, SKBR-3, MCF-7, MCF-7/ADR, MDA-MB-231 cell lines was assessed under incubation conditions with 64 variants of SAHA and DOX combinations using the MTT assay. This made it possible to determine the effect of interactions of SAHA/DOX combinations (antagonistic, additive, synergistic), as well as calculate the SAHA/DOX synergy index using the Loewe additivity model. The effect of SAHA/DOX ratios with the highest synergistic index for each tumor cell line was confirmed using the Chou-Talalay method. It was shown that the SAHA/DOX combination exhibited the greatest synergism in relation to HCC-1954, MCF-7/ADR and SKBR-3 cell lines belonging to the HER2-positive subtype. The average value of SAHA/DOX ratio with the highest synergy against breast cancer cells was 30:1 (SAHA to DOX, respectively). The ability of SAHA/DOX combination to effectively trigger apoptosis was confirmed in the most sensitive to SAHA/DOX therapy HCC-1954 cells. Thus, the Loewe model made it possible to identify the drug combination with the highest synergistic anticancer effect, which was confirmed using Chou-Talalay method. The data obtained demonstrates great potential of SAHA/DOX combination (30:1) for the treatment of HER2-positive breast cancer.

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.

Biocompatible, biodegradable polymers are actively used as drug delivery systems and as tissue engineering scaffolds. The hydrothermal aging of polymers, including degradation of the microstructure and changes of mechanical properties directly depends on environmental conditions. In vitro studies in a model media cannot contain and describe all the factors influencing the polymer degradation in a living organism. It seems promising to study the processes of changes in the microstructure and elastic properties of polymer implants in vivo in dynamics. Here, we present data from the application of new experimental equipment for high-resolution ultrasound imaging of polymer degradation in vivo. Ultrasonic results include images of the transformation of volumetric microstructure and changes in elastic properties in dynamics. The method was verified on a rapidly degradable polymer poly(D,L-lactide-co-glycolide). We assess and compare the evolution of volume microstructure, elastic properties and molecular weight of the polymer weekly for 1.5 months of incubation in vitro and in vivo. We found that the in vivo degradation process occurs with a delay of 2 weeks compared to the hydrothermal aging in vitro.

The objects of the present study are nanoparticles (NPs) based on a copolymer of lactic and glycolic acids (PLGA), loaded with the anticancer drug doxorubicin (DOX-NP) and histone deacetylase inhibitor vorinostat (SAHA-NP) and developed for breast cancer treatment [...]

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.

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.

Background: Serious side effects caused by paclitaxel formulation, containing toxic solubilizer Cremophor® EL, and its nonspecific accumulation greatly limit clinical paclitaxel application. Aim: To design paclitaxel-loaded copolymer of lactic and glycolic acids nanoparticles decorated with alpha-fetoprotein third domain (rAFP3d-NP) to increase paclitaxel safety profile. Methods: rAFP3d-NP was obtained via carbodiimide technique. Results: The particles were characterized with high paclitaxel loading content of 5% and size of 280 nm. rAFP3d-NP revealed biphasic profile with 67% release of paclitaxel during 220 h. Increased area under the curveinf and mean residence time values after rAFP3d-NP administration confirmed prolonged blood circulation compared with paclitaxel. rAFP3d-NP demonstrated significant tumor growth inhibition at 4T1 and SKOV-3 models. Conclusion: rAFP3d-NP is a promising delivery system for paclitaxel and can be applied similarly for delivery of other hydrophobic drugs.

Introduction. The use of the anticancer drug paclitaxel is limited due to its high toxicity and lipophilicity. A new polymer composition of paclitaxel has been proposed, which provides targeted transport of the drug into tumor cells and improves its safety. Aim. Method development for preparation of a novel paclitaxel formulation consisting of a conjugate of PLGA nanoparticles with the third domain of alpha-fetoprotein. Materials and methods. The object of this study is paclitaxel-loaded nanoparticles based on a copolymer of lactic and glycolic acids, the surface of which is modified with a vector molecule - the recombinant third domain of alpha-fetoprotein. Nanoparticles were obtained by single emulsification method and precipitation. Conjugation with a protein molecule was performed by the carbodiimide method. The analysis of the obtained nanoparticles was carried out using dynamic and electrophoretic light scattering, high performance liquid chromatography, dialysis membrane method. Results and discussion. Synthesis of paclitaxel-loaded nanoparticles based on a copolymer of lactic and glycolic acids and its conjugation optimization under varying a wide range of conditions have been carried out. The resulting conjugate had an average diameter of 280 ± 12 nm. The conjugation efficiency was 95 %. The release of paclitaxel from the polymer matrix in the release medium was 65 % in 220 h. Conclusions. A method of obtaining and substantiating the composition of the original nanosized form of paclitaxel is proposed. The possibility of prolonged release of paclitaxel from the polymer matrix has been shown.

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.

Potential applications of cold hybrid plasma for polymeric materials biocompatibility improvement is considered. Oxygen plasma was generated in the special plasma chemical reactor of hybrid type [1] by joint action of a continuous or intermittent electron beam and RF-gas discharge on gaseous media at moderate pressures (0.1-10 Torr). The main hybrid reactor advantages are as follows: