The modern livestock industry incorporates widely used antibiotic growth promoters into animal feed at sub-therapeutic levels to enhance growth performance and feed efficiency. However, this practice contributes to the emergence of antibiotic-resistant pathogens in livestock, which may be transmitted to humans through the food chain, thereby diminishing the efficacy of antibiotics in treating bacterial infections. Current research explores the potential of essential oils from derived medicinal plants as alternative phytobiotics. This review examines modern encapsulation strategies that incorporate essential oils into natural-origin matrices to improve their stability and control their release both in vitro and in vivo. We discuss a range of encapsulation approaches utilizing polysaccharides, gums, proteins, and lipid-based carriers. This review highlights the increasing demand for antibiotic alternatives in animal nutrition driven by regulatory restrictions, and the potential benefits of essential oils in enhancing feed palatability and stabilizing the intestinal microbiome in monogastric animals and ruminants. Additionally, we address the economic viability and encapsulation efficiency of different matrix formulations.

Mathematical models are widely used to assess drug synergy. However, identifying the most effective combination ratio represents a major challenge. In this study, we applied two established mathematical models to assess synergism and optimize the ratio of vorinostat (SAHA) and doxorubicin (DOX) in vitro for breast cancer (BC) models. BC poses a significant challenge in oncology due to high incidence rates, mortality, and drug resistance. Therefore, developing new treatment strategies is essential to improve anticancer therapeutic outcomes. While polychemotherapy offers significant clinical benefits by enhancing efficacy and reducing toxicity, no consensus exists on optimal drug ratio determination. We evaluated synergism across a broad panel of BC cell lines using the Bliss model and the Chou-Talalay method. Both methods identified a similar pattern of combination synergism. Based on synergy index calculations and drug ratio determination, we found the Bliss model more suitable for determining the optimal SAHA/DOX ratio. The most effective drugs ratio was calculated as 30:1 of SAHA to DOX, respectively. This combination showed strong efficacy in both 2D and 3D cancer models. Our results highlight the potential value of synergy-based computational tools to guide effective combination therapies in BC and justify further preclinical and in vivo validation of the SAHA/DOX combination.

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.

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.

A novel amphiphilic cationic chlorin e(6) derivative was investigated as a promising photosensitizer for photodynamic therapy. Two cationic -N(CH3)(3)(+) groups on the periphery of the macrocycle provide additional hydrophilization of the molecule and ensure its electrostatic binding to the mitochondrial membranes and bacterial cell walls. The presence of a hydrophobic phytol residue in the same molecule results in its increased affinity towards the phospholipid membranes while decreasing its stability towards aggregation in aqueous media. In organic media, this chlorin e(6) derivative is characterized by a singlet oxygen quantum yield of 55%. Solubilization studies in different polymer- and surfactant-based supramolecular systems revealed the effective stabilization of this compound in a photoactive monomolecular form in micellar nonionic surfactant solutions, including Tween-80 and Cremophor EL. A novel cationic chlorin e(6) derivative also demonstrates effective binding towards serum albumin, which enhances its bioavailability and promotes effective accumulation within the target tissues. Laser confocal scanning microscopy demonstrates the rapid intracellular accumulation and distribution of this compound throughout the cells. Together with low dark toxicity and a rather good photostability, this compound demonstrates significant phototoxicity against HeLa cells causing cellular damage most likely through reactive oxygen species generation. These results demonstrate a high potential of this derivative for application in photodynamic therapy.

Photodynamic therapy (PDT) in oncology is characterized by low invasiveness, minimal side effects, and little tissue scarring. Increasing the selectivity of PDT agents toward a cellular target is a new approach intended to improve this method. This study is devoted to the design and synthesis of a new conjugate based on meso-arylporphyrin with a low-molecular-weight tyrosine kinase inhibitor, Erlotinib. A nano-formulation based on Pluronic F127 micelles was obtained and characterized. The photophysical and photochemical properties and biological activity of the studied compounds and their nano-formulation were studied. A significant, 20–40-fold difference between the dark and photoinduced activity was achieved for the conjugate nanomicelles. After irradiation, the studied conjugate nanomicelles were 1.8 times more toxic toward the EGFR-overexpressing cell line MDA-MB-231 compared to the conditionally normal NKE cells. The IC50 was 0.073 ± 0.014 μM for the MDA-MB-231 cell line and 0.13 ± 0.018 μM for NKE cells after irradiation for the target conjugate nanomicelles.

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.

The calcium-carbonate-induced mineralization of multilayer shells of emulsion capsules, formed using layer-by-layer assembly of polyelectrolytes, has been investigated. Optimal conditions for forming microcapsules with a core from shea butter and an organic–inorganic shell from synthetic polyelectrolytes and calcium carbonate are found. The shell morphology and stability of capsules in an aqueous suspension upon heating are investigated, and their cytotoxicity for human fibroblast cells is estimated. It is shown that mineralization of emulsion polyelectrolyte capsules by calcium carbonate in the form of vaterite strengthens the capsule walls and increases their biocompatibility.

This work is devoted to development of a method for synthesis of vorinostat-loaded nanoparticles based on a copolymer of lactic and glycolic acids. The technology of synthesis of polymeric particles was optimized with the help of the Box–Behnken design. The nanoparticles synthesized by using the optimized technology had a spherical shape, which was confirmed by transmission electron microscopy. The average diameter of the nanoparticles was 196 nm, the polydispersity index was 0.089, and the zeta potential was –22.3 mV. Drug loading in the nanoparticles was 0.91 wt

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 [...]

Previous studies have demonstrated the applicability of alpha-fetoprotein or its receptor-binding domain fused to the 6-histidine tag at the C-terminus (rAFP3D-His6) as vectors for targeted delivery of antitumor agents. The His6 tag is undesirable for further preclinical trials. Therefore, we designed a recombinant protein rAFP3D without any affine tags and assessed its functional activity. The protein was produced as inclusion bodies in Escherichia coli BL21 (DE3) cells. Optimal conditions for washing inclusion bodies and refolding the target protein were selected. We used a saturated (NH4)2SO4 solution at the primary purification stage to precipitate the main fraction of nontarget proteins. The second purification step included hydrophobic interaction chromatography using butyl-cellulose. The identity of the protein sequence was confirmed by tandem mass spectrometry. Circular dichroism demonstrated the authenticity of the secondary structure of the recombinant protein. MCF-7 tumor cells actively internalized fluorescently labeled rAFP3D. These results indicate that rAFP3D can be used for targeted drug delivery.

Capsules with shells based on nanoparticles of different nature co-assembled at the interface of liquid phases of emulsion are promising carriers of lipophilic drugs. To obtain such capsules, theoretically using the Derjaguin–Landau–Verwey–Overbeek (DLVO) theory and experimentally using dynamic light-scattering (DLS) and transmission electron microscopy (TEM) methods, the interaction of like-charged silica nanoparticles and detonation nanodiamonds in an aqueous solution was studied and their ratios selected for the formation of submicron-sized colloidosomes. The resulting colloidosomes were modified with additional layers of nanoparticles and polyelectrolytes, applying LbL technology. As a model anti-cancer drug, thymoquinone was loaded into the developed capsules, demonstrating a significant delay of the release as a result of colloidosome surface modification. Fluorescence flow cytometry and confocal laser scanning microscopy showed efficient internalization of the capsules by MCF7 cancer cells. The obtained results demonstrated a high potential for nanomedicine application in the field of the drug-delivery system development.

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.