Nanoparticle Compounds Research Articles

NANO.PTML model for read-across prediction of nanosystems in neurosciences. computational model and experimental case of study

Neurodegenerative diseases involve progressive neuronal death. Traditional treatments often struggle due to solubility, bioavailability, and crossing the Blood-Brain Barrier (BBB). Nanoparticles (NPs) in biomedical field are garnering growing attention as neurodegenerative disease drugs (NDDs) carrier to the central nervous system. Here, we introduced computational and experimental analysis. In the computational study, a specific IFPTML technique was used, which combined Information Fusion (IF) + Perturbation Theory (PT) + Machine Learning (ML) to select the most promising Nanoparticle Neuronal Disease Drug Delivery (N2D3) systems. For the application of IFPTML model in the nanoscience, NANO.PTML is used. IF-process was carried out between 4403 NDDs assays and 260 cytotoxicity NP assays conducting a dataset of 500,000 cases. The optimal IFPTML was the Decision Tree (DT) algorithm which shown satisfactory performance with specificity values of 96.4% and 96.2%, and sensitivity values of 79.3% and 75.7% in the training (375k/75%) and validation (125k/25%) set. Moreover, the DT model obtained Area Under Receiver Operating Characteristic (AUROC) scores of 0.97 and 0.96 in the training and validation series, highlighting its effectiveness in classification tasks. In the experimental part, two samples of NPs (Fe3O4_A and Fe3O4_B) were synthesized by thermal decomposition of an iron(III) oleate (FeOl) precursor and structurally characterized by different methods. Additionally, in order to make the as-synthesized hydrophobic NPs (Fe3O4_A and Fe3O4_B) soluble in water the amphiphilic CTAB (Cetyl Trimethyl Ammonium Bromide) molecule was employed. Therefore, to conduct a study with a wider range of NP system variants, an experimental illustrative simulation experiment was performed using the IFPTML-DT model. For this, a set of 500,000 prediction dataset was created. The outcome of this experiment highlighted certain NANO.PTML systems as promising candidates for further investigation. The NANO.PTML approach holds potential to accelerate experimental investigations and offer initial insights into various NP and NDDs compounds, serving as an efficient alternative to time-consuming trial-and-error procedures.

On the additive artificial intelligence-based discovery of nanoparticle neurodegenerative disease drug delivery systems.

Neurodegenerative diseases are characterized by slowly progressing neuronal cell death. Conventional drug treatment strategies often fail because of poor solubility, low bioavailability, and the inability of the drugs to effectively cross the blood-brain barrier. Therefore, the development of new neurodegenerative disease drugs (NDDs) requires immediate attention. Nanoparticle (NP) systems are of increasing interest for transporting NDDs to the central nervous system. However, discovering effective nanoparticle neuronal disease drug delivery systems (N2D3Ss) is challenging because of the vast number of combinations of NP and NDD compounds, as well as the various assays involved. Artificial intelligence/machine learning (AI/ML) algorithms have the potential to accelerate this process by predicting the most promising NDD and NP candidates for assaying. Nevertheless, the relatively limited amount of reported data on N2D3S activity compared to assayed NDDs makes AI/ML analysis challenging. In this work, the IFPTML technique, which combines information fusion (IF), perturbation theory (PT), and machine learning (ML), was employed to address this challenge. Initially, we conducted the fusion into a unified dataset comprising 4403 NDD assays from ChEMBL and 260 NP cytotoxicity assays from journal articles. Through a resampling process, three new working datasets were generated, each containing 500,000 cases. We utilized linear discriminant analysis (LDA) along with artificial neural network (ANN) algorithms, such as multilayer perceptron (MLP) and deep learning networks (DLN), to construct linear and non-linear IFPTML models. The IFPTML-LDA models exhibited sensitivity (Sn) and specificity (Sp) values in the range of 70% to 73% (>375,000 training cases) and 70% to 80% (>125,000 validation cases), respectively. In contrast, the IFPTML-MLP and IFPTML-DLN achieved Sn and Sp values in the range of 85% to 86% for both training and validation series. Additionally, IFPTML-ANN models showed an area under the receiver operating curve (AUROC) of approximately 0.93 to 0.95. These results indicate that the IFPTML models could serve as valuable tools in the design of drug delivery systems for neurosciences.

Intracellular Activity of Poly (DL-Lactide-co-Glycolide) Nanoparticles Encapsulated with Prothionamide, Pyrazinamide, Levofloxacin, Linezolid, or Ethambutol on Multidrug-Resistant Mycobacterium tuberculosis.

Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is a major cause of death amongst tuberculosis patients. Nanomedicine avoids some limitations of conventional drug treatment and increases therapeutic efficacy against bacterial infections. However, the effect of anti-TB drug nanoparticle (NP) compounds in anti-TB regimens against MDR-TB remains unclear. The objective of this article is to prepare levofloxacin, linezolid, ethambutol, prothionamide, and pyrazinamide encapsulated NPs and to evaluate their therapeutic efficacy against MDR-TB in macrophages. Drug-loaded PLGA NPs were prepared by the multiple emulsion method. The colocalization, intracellular release, and anti-TB activity of these NPs were investigated on cultured macrophages. The immune phenotype of the macrophages, including their mitochondrial membrane potential, reactive oxygen species (ROS), and nitric oxide (NO) production, was evaluated following treatment with NPs or free drug compounds. All drug-loaded PLGA NPs were spherical in shape, 150 to 210 nm in size, and showed 14.22% to 43.51% encapsulation efficiencies and long-duration release. Drug-loaded PLGA NPs were mainly distributed in the cytoplasm of macrophages, showed high cellular compatibility, and maintained their concentration for at least 13 days. Compared with the free drug compounds, the number of colonies after exposure to PLGA NP compounds was significantly less. The enhanced antibacterial activity of the NP compounds may be due to the enhanced levels of ROS and NO and the increased early apoptosis stress within M. tuberculosis-infected macrophages additionally. The application of PLGA NP compounds not only enhances drug efficacy but also induces innate bactericidal events in macrophages, confirming this as a promising approach for MDR-TB therapy.

Threonine-Based Stimuli-Responsive Nanoparticles with Aggregation-Induced Emission-Type Fixed Cores for Detection of Amines in Aqueous Solutions.

Stimuli-responsive polymeric nanoparticles (NPs) exhibit reversible changes in the dispersion or aggregation state in response to external stimuli. In this context, we designed and synthesized core-shell NPs with threonine-containing weak polyelectrolyte shells and fluorescent cross-linked cores, which are applicable for the detection of pH changes and amine compounds in aqueous solution. Stable and uniform NP(dTh) and NP(Fl), consisting of fluorescent symmetric diphenyl dithiophene (dTh) and diphenyl fluorene (Fl) cross-linked cores, were prepared by site-selective Suzuki coupling reactions in self-assembled block copolymer. NP(Fl) with the Fl unit in the core showed a high fluorescence intensity in different solvents, which is regarded as an aggregation-induced emission-type NP showing strong emission in aggregated states in the cross-linked core. Unimodal NPs were observed in water at different pH values, and the diameter of NP(Fl) changed from 122 (pH = 2) to 220 nm (pH = 11). Furthermore, pH-dependent changes of the fluorescence peak positions and intensities were detected, which may be due to the core aggregation derived from the deprotonation of the threonine-based shell fragment. Specific interactions between the threonine-based shell of NP(Fl) and amine compounds (triethylamine and p-phenylenediamine) resulted in fluorescence quenching, suggesting the feasibility of fluorescent amine detection.

Актуальные аспекты применения химически синтезированных соединений наночастиц серебра в животноводстве и агрохимии

Рассмотрены сферы применения наночастиц (НЧ) серебра в сельском хозяйстве. Приведен обзор литературы, посвященной использованию соединений НЧ серебра в животноводстве при кормлении и лечении сельскохозяйственных животных. Рассмотрены основные направления внедрения наносеребра в практику при защите культурных растений и их возделывании. Авторы представляют свои основные результаты исследований в этой области. Препарат “Арговит”, созданный на основе НЧ серебра и поливинилпирролидона, снижает антибиотикочувствительность, адгезивную и антилизоцимную активности патогенов родов Enterococcus, Salmonella и Escherichia, которые определяют возникновение, развитие и проявление инфекционных болезней у животных. Обнаружено, что нанокомпозиты серебра, представляющие собой НЧ серебра, погруженные в матрицы из природного полисахарида (арабиногалактана) или гуминовых веществ, обладают антибактериальным эффектом к бактерии, вызывающей кольцевую гниль картофеля. При этом нанокомпозиты оказывают стимулирующее воздействие на растения картофеля in vitro. Представленные сведения подтверждают перспективность широкого применения НЧ серебра в сельском хозяйстве.

Antibacterial activity of iron oxide, iron nitride, and tobramycin conjugated nanoparticles against Pseudomonas aeruginosa biofilms

BackgroundNovel methods are necessary to reduce morbidity and mortality of patients suffering from infections with Pseudomonas aeruginosa. Being the most common infectious species of the Pseudomonas genus, P. aeruginosa is the primary Gram-negative etiology responsible for nosocomial infections. Due to the ubiquity and high adaptability of this species, an effective universal treatment method for P. aeruginosa infection still eludes investigators, despite the extensive research in this area.ResultsWe report bacterial inhibition by iron-oxide (nominally magnetite) nanoparticles (NPs) alone, having a mean hydrodynamic diameter of ~ 16 nm, as well as alginate-capped iron-oxide NPs. Alginate capping increased the average hydrodynamic diameter to ~ 230 nm. We also investigated alginate-capped iron-oxide NP-drug conjugates, with a practically unchanged hydrodynamic diameter of ~ 232 nm. Susceptibility and minimum inhibitory concentration (MIC) of the NPs, NP-tobramycin conjugates, and tobramycin alone were determined in the PAO1 bacterial colonies. Investigations into susceptibility using the disk diffusion method were done after 3 days of biofilm growth and after 60 days of growth. MIC of all compounds of interest was determined after 60-days of growth, to ensure thorough establishment of biofilm colonies.ConclusionsPositive inhibition is reported for uncapped and alginate-capped iron-oxide NPs, and the corresponding MICs are presented. We report zero susceptibility to iron-oxide NPs capped with polyethylene glycol, suggesting that the capping agent plays a major role in enabling bactericidal ability in of the nanocomposite. Our findings suggest that the alginate-coated nanocomposites investigated in this study have the potential to overcome the bacterial biofilm barrier. Magnetic field application increases the action, likely via enhanced diffusion of the iron-oxide NPs and NP-drug conjugates through mucin and alginate barriers, which are characteristic of cystic-fibrosis respiratory infections. We demonstrate that iron-oxide NPs coated with alginate, as well as alginate-coated magnetite–tobramycin conjugates inhibit P. aeruginosa growth and biofilm formation in established colonies. We have also determined that susceptibility to tobramycin decreases for longer culture times. However, susceptibility to the iron-oxide NP compounds did not demonstrate any comparable decrease with increasing culture time. These findings imply that iron-oxide NPs are promising lower-cost alternatives to silver NPs in antibacterial coatings, solutions, and drugs, as well as other applications in which microbial abolition or infestation prevention is sought.

The Current Aspects of Using Chemically Synthesized Compounds of Silver Nanoparticles in Animal Husbandry and Agrochemistry

The areas of silver nanoparticle (NPs) application in agriculture are considered in the present paper. Publications dedicated to the use of silver NP compounds as feed components and drugs for farm animals are reviewed. The main directions of nanosilver introduction into the practice of cultivated plant protection and growing are considered. The authors present the major results of their own studies in this area. Argovit with silver NPs and polyvinylpyrrolidone as the main components reduced the antibiotic resistance and the adhesive and anti-lysozyme activities of pathogens from the genera Enterococcus, Salmonella, and Escherichia, which determine the emergence, development, and manifestations of infectious diseases in animals. Silver nanocomposites (NCs) that consist of silver NPs embedded in matrices of a natural polysaccharide (arabinogalactan) or humic substances were shown to have an antibacterial effect on bacteria that cause potato ring rot. Moreover, the NCs had a stimulatory effect on potato plants in vitro. The presented data confirm the high potential of wide use of silver NPs in agriculture.

Evaluation of dual P-gp-BCRP inhibitors as nanoparticle formulation

Overcoming multidrug resistance (MDR) in cancer is a major challenge and efforts are on-going to develop inhibitors against the most characterized and ubiquitous MDR transporters: P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP1) and breast cancer resistance protein (BCRP). Recently reported, two 4-anilinoquinazolines (compounds 1 and 2), demonstrate potential MDR reversal activity against BCRP and to a lesser extent, P-gp. In this work, we formulated the compounds as polymeric nanoparticles (NPs) and assessed their MDR inhibitory activity in relevant BCRP and P-gp over-expressing cell line models. Particles in the size range 300–365nm with a loading efficiency of 69% (compound 1 NP) and 77% (compound 2 NP) respectively were obtained. BCRP inhibition was observed in Hoechst 33342 and pheophorbide A assays while P-gp inhibition was evaluated in calcein AM and rhodamine-123 assays. In cytotoxicity studies, while BCRP expressing cells showed complete reversal of drug resistance in nearly all treatment groups (both compounds and their respective NP); a higher reversal in NP treated group was obtained as compared with inhibitory compound treated group in P-gp expressing cells. These results demonstrate promising inhibitory activity of both formulations, especially against P-gp expressing cells; which is possibly due to a prolonged presence of encapsulated compounds in NPs and consequently a prolonged sensitization of transmembrane drug transporter. These formulations can therefore be considered as dual-transporter inhibitors and it is imperative to investigate both inhibitors in animal models of MDR owing to the presence of multiple efflux transporters in several cancer models.