Insights into the Microbicidal, Antibiofilm, Antioxidant and Toxicity Profile of New O-Aryl-Carbamoyl-Oxymino-Fluorene Derivatives.

The unprecedented increase in microbial resistance rates to all current drugs raises an acute need for the design of more effective antimicrobial strategies. Moreover, the importance of oxidative stress due to chronic inflammation in infections with resistant bacteria represents a key factor for the development of new antibacterial agents with potential antioxidant effects. Thus, the purpose of this study was to bioevaluate new O-aryl-carbamoyl-oxymino-fluorene derivatives for their potential use against infectious diseases. With this aim, their antimicrobial effect was evaluated using quantitative assays (minimum inhibitory/bactericidal/biofilms inhibitory concentrations) (MIC/MBC/MBIC), the obtained values being 0.156-10/0.312-10/0.009-1.25 mg/mL), while some of the involved mechanisms (i.e., membrane depolarization) were investigated by flow cytometry. The antioxidant activity was evaluated by studying the scavenger capacity of DPPH and ABTS•+ radicals and the toxicity was tested in vitro on three cell lines and in vivo on the crustacean Artemia franciscana Kellog. The four compounds derived from 9H-fluoren-9-one oxime proved to exhibit promising antimicrobial features and particularly, a significant antibiofilm activity. The presence of chlorine induced an electron-withdrawing effect, favoring the anti-Staphylococcus aureus and that of the methyl group exhibited a +I effect of enhancing the anti-Candida albicans activity. The IC50 values calculated in the two toxicity assays revealed similar values and the potential of these compounds to inhibit the proliferation of tumoral cells. Taken together, all these data demonstrate the potential of the tested compounds to be further used for the development of novel antimicrobial and anticancer agents.

Carriage of ESBL-producing Enterobacterales in wastewater treatment plant workers and surrounding residents - the AWARE Study.

To investigate whether wastewater treatment plant (WWTP) workers and residents living in close proximity to a WWTP have elevated carriage rates of ESBL-producing Enterobacterales, as compared to the general population. From 2018 to 2020, we carried out a cross-sectional study in Germany, the Netherlands, and Romania among WWTP workers (N = 344), nearby residents (living ≤ 300 m away from WWTPs; N = 431) and distant residents (living ≥ 1000 m away = reference group; N = 1165). We collected information on potential confounders via questionnaire. Culture of participants' stool samples was performed with ChromID®-ESBL agar plates and species identification with MALDI-TOF-MS. We used logistic regression to estimate the odds ratio (OR) for carrying ESBL-producing E. coli (ESBL-EC). Sensitivity analyses included stratification by country and interaction models using country as secondary exposure. Prevalence of ESBL-EC was 11% (workers), 29% (nearby residents), and 7% (distant residents), and higher in Romania (28%) than in Germany (7%) and the Netherlands (6%). Models stratified by country showed that within the Romanian population, WWTP workers are about twice as likely (aOR = 2.34, 95% CI: 1.22-4.50) and nearby residents about three times as likely (aOR = 3.17, 95% CI: 1.80-5.59) to be ESBL-EC carriers, when compared with distant residents. In stratified analyses by country, we found an increased risk for carriage of ESBL-EC in Romanian workers and nearby residents. This effect was higher for nearby residents than for workers, which suggests that, for nearby residents, factors other than the local WWTP could contribute to the increased carriage.

Dysbiosis in the Development of Type I Diabetes and Associated Complications: From Mechanisms to Targeted Gut Microbes Manipulation Therapies.

Globally, we are facing a worrying increase in type 1 diabetes mellitus (T1DM) incidence, with onset at younger age shedding light on the need to better understand the mechanisms of disease and step-up prevention. Given its implication in immune system development and regulation of metabolism, there is no surprise that the gut microbiota is a possible culprit behind T1DM pathogenesis. Additionally, microbiota manipulation by probiotics, prebiotics, dietary factors and microbiota transplantation can all modulate early host-microbiota interactions by enabling beneficial microbes with protective potential for individuals with T1DM or at high risk of developing T1DM. In this review, we discuss the challenges and perspectives of translating microbiome data into clinical practice. Nevertheless, this progress will only be possible if we focus our interest on developing numerous longitudinal, multicenter, interventional and double-blind randomized clinical trials to confirm their efficacy and safety of these therapeutic approaches.

Chemical Composition, Antipathogenic and Cytotoxic Activity of the Essential Oil Extracted from Amorpha fruticosa Fruits.

The purpose of this paper was to characterize and investigate the antimicrobial potential of Amorpha fruticosa fruits essential oil (EO). The EO was extracted by hydrodistillation, analyzed by GC-MS, and then evaluated for its interaction with microbial and mammalian cells. The antimicrobial activity was assessed against bacterial and fungal strains, in a planktonic and adherent growth state, using qualitative and quantitative assays. The main components identified in A. fruticosa fruits EO were δ-cadinene, γ-muurolene, and α-muurolene. The Gram-positive strains proved to be more susceptible than Gram-negative bacteria and fungal strains. The EO exhibited good antibiofilm activity, inhibiting the microbial adherence to the inert (96-well plates and Foley catheter section) and cellular substrata. The flow cytometry analysis revealed as one of the possible mechanisms of antimicrobial action the alteration of cell membrane hydrophobicity. The cytotoxicity on the L929 cell line occurred at concentrations higher than 0.3 mg/mL. Taken together, our results demonstrate that A. fruticosa fruits EO contains active compounds with selective inhibitory effect on different microbial strains in planktonic and biofilm growth state, explained at least partially by the interference with microbial membranes due to their hydrophobic character.

Synthesis and Biological Evaluation of New N-Acyl-α-amino Ketones and 1,3-Oxazoles Derivatives.

In order to develop novel bioactive substances with potent activities, some new valine-derived compounds incorporating a 4-(phenylsulfonyl)phenyl fragment, namely, acyclic precursors from N-acyl-α-amino acids and N-acyl-α-amino ketones classes, and heterocycles from the large family of 1,3-oxazole-based compounds, were synthesized. The structures of the new compounds were established using elemental analysis and spectral (UV-Vis, FT-IR, MS, NMR) data, and their purity was checked by reversed-phase HPLC. The newly synthesized compounds were evaluated for their antimicrobial and antibiofilm activities, for toxicity on D. magna, and by in silico studies regarding their potential mechanism of action and toxicity. The 2-aza-3-isopropyl-1-[4-(phenylsulfonyl)phenyl]-1,4-butanedione 4b bearing a p-tolyl group in 4-position exhibited the best antibacterial activity against the planktonic growth of both Gram-positive and Gram-negative strains, while the N-acyl-α-amino acid 2 and 1,3-oxazol-5(4H)-one 3 inhibited the Enterococcus faecium biofilms. Despite not all newly synthesized compounds showing significant biological activity, the general scaffold allows several future optimizations for obtaining better novel antimicrobial agents by the introduction of various substituents on the phenyl moiety at position 5 of the 1,3-oxazole nucleus.

Synthesis, In Silico and In Vitro Evaluation of Antimicrobial and Toxicity Features of New 4-[(4-Chlorophenyl)sulfonyl]benzoic Acid Derivatives.

The multi-step synthesis, physico-chemical characterization, and biological activity of novel valine-derived compounds, i.e., N-acyl-α-amino acids, 1,3-oxazol-5(4H)-ones, N-acyl-α-amino ketones, and 1,3-oxazoles derivatives, bearing a 4-[(4-chlorophenyl)sulfonyl]phenyl moiety are reported here. The structures of the newly synthesized compounds were confirmed by spectral (UV-Vis, FT-IR, MS, 1H- and 13C-NMR) data and elemental analysis results, and their purity was determined by RP-HPLC. The new compounds were assessed for their antimicrobial activity and toxicity to aquatic crustacean Daphnia magna. Also, in silico studies regarding their potential mechanism of action and toxicity were performed. The antimicrobial evaluation revealed that the 2-{4-[(4-chlorophenyl)sulfonyl]benzamido}-3-methylbutanoic acid and the corresponding 1,3-oxazol-5(4H)-one exhibited antimicrobial activity against Gram-positive bacterial strains and the new 1,3-oxazole containing a phenyl group at 5-position against the C. albicans strain.

New O-Aryl-Carbamoyl-Oxymino-Fluorene Derivatives with MI-Crobicidal and Antibiofilm Activity Enhanced by Combination with Iron Oxide Nanoparticles.

Antimicrobial resistance is one of the major public health threats at the global level, urging the search for new antimicrobial molecules. The fluorene nucleus is a component of different bioactive compounds, exhibiting diverse pharmacological actions. The present work describes the synthesis, chemical structure elucidation, and bioactivity of new O-aryl-carbamoyl-oxymino-fluorene derivatives and the contribution of iron oxide nanoparticles to enhance the desired biological activity. The antimicrobial activity assessed against three bacterial and fungal strains, in suspension and biofilm growth state, using a quantitative assay, revealed that the nature of substituents on the aryl moiety are determinant for both the spectrum and intensity of the inhibitory effect. The electron-withdrawing inductive effect of chlorine atoms enhanced the activity against planktonic and adhered Staphylococcus aureus, while the +I effect of the methyl group enhanced the anti-fungal activity against Candida albicans strain. The magnetite nanoparticles have substantially improved the antimicrobial activity of the new compounds against planktonic microorganisms. The obtained compounds, as well as the magnetic core@shell nanostructures loaded with these compounds have a promising potential for the development of novel antimicrobial strategies.

New Substituted Benzoylthiourea Derivatives: From Design to Antimicrobial Applications.

The increasing threat of antimicrobial resistance to all currently available therapeutic agents has urged the development of novel antimicrobials. In this context, a series of new benzoylthiourea derivatives substituted with one or more fluorine atoms and with the trifluoromethyl group have been tested, synthesized, and characterized by IR, NMR, CHNS and crystal X-ray diffraction. The molecular docking has provided information regarding the binding affinity and the orientation of the new compounds to Escherichia coli DNA gyrase B. The docking score predicted the antimicrobial activity of the studied compounds, especially against E. coli, which was further demonstrated experimentally against planktonic and biofilm embedded bacterial and fungal cells. The compounds bearing one fluorine atom on the phenyl ring have shown the best antibacterial effect, while those with three fluorine atoms exhibited the most intensive antifungal activity. All tested compounds exhibited antibiofilm activity, correlated with the trifluoromethyl substituent, most favorable in para position.

In Silico and In Vitro Experimental Studies of New Dibenz[b,e]oxepin-11(6H)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents.

In a drug-repurposing-driven approach for speeding up the development of novel antimicrobial agents, this paper presents for the first time in the scientific literature the synthesis, physico-chemical characterization, in silico analysis, antimicrobial activity against bacterial and fungal strains in planktonic and biofilm growth state, as well as the in vitro cytotoxicity of some new 6,11-dihydrodibenz[b,e]oxepin-11(6H)one O-(arylcarbamoyl)oximes. The structures of intermediary and final substances (compounds 7a-j) were confirmed by 1H-NMR, 13C-NMR and IR spectra, as well as by elemental analysis. The in silico bioinformatic and cheminformatic studies evidenced an optimal pharmacokinetic profile for the synthesized compounds 7a-j, characterized by an average lipophilic character predicting good cell membrane permeability and intestinal absorption; low maximum tolerated dose for humans; potassium channels encoded by the hERG I and II genes as potential targets and no carcinogenic effects. The obtained compounds exhibited a higher antimicrobial activity against the planktonic Gram-positive Staphylococcus aureus and Bacillus subtilis strains and the Candida albicans fungal strain. The obtained compounds also inhibited the ability of S. aureus, B. subtilis, Escherichia coli and C. albicans strains to colonize the inert substratum, accounting for their possible use as antibiofilm agents. All the active compounds exhibited low or acceptable cytotoxicity levels on the HCT8 cells, ensuring the potential use of these compounds for the development of new antimicrobial drugs with minimal side effects on the human cells and tissues.

Multifunctional Hydroxyapatite Coated with Arthemisia absinthium Composites.

There is significant research showing that essential oils extracted from the plants have antibacterial effects. The purpose of this study was to develop a biocomposite based on hydroxyapatite coated with Artemisia absinthium essential oil and to highlight its antibacterial activity. Therefore, present studies are aimed at developing new materials combining hydroxyapatite with Artemisia absinthium essential oil, in order to avoid postoperative infections. The purpose of this work is to highlight the antimicrobial properties of the Artemisia absinthium essential oil-hydroxyapatite composites obtained by a simple method and at low costs. The structural properties and antimicrobial efficiency of the Artemisia absinthium essential oil-hydroxyapatite composite have been studied. The samples based on Artemisia absinthium essential oil analyzed in this study showed that wormwood essential oil presented the highest efficacy against the fungal strain of C. parapsilosis. It has been shown that wormwood essential oil has a strong antimicrobial effect against the microbial strains tested in this study. Furthermore, the antimicrobial properties of the biocomposites based on hydroxyapatite and essential oil are due to the presence of the essential oil in the samples.

Synthesis, Structural Characterization, Antimicrobial Activity, and In Vitro Biocompatibility of New Unsaturated Carboxylate Complexes with 2,2'-Bipyridine.

The synthesis, structural characterization, cytotoxicity, and antimicrobial properties of four new complexes formed by employing acrylate anion and 2,2'-bipyridine are reported herein. X-ray crystallography revealed the trinuclear nature of [Mn3(2,2'-bipy)2(C3H3O2)6] (1), meanwhile complexes with general formula [M(2,2'-bipy)(C3H3O2)2(H2O)x]∙yH2O ((2) M: Ni, x = 1, y = 0; (3) M: Cu, x = 1, y = 0; (4) M: Zn, x = 0, y = 1; 2,2'-bipy: 2,2'-bipyridine; C3H3O2: acrylate anion) were shown to be mononuclear. The lowest minimum inhibitory concentration (MIC) of 128 µg mL-1 was recorded for all four tested complexes against Candida albicans, for complex (3) against Escherichia coli, and for complex (4) against Staphylocococcus aureus. Compounds (3) and (4) were also potent efflux pumps activity inhibitors (EPI), proving their potential for use in synergistic combinations with antibiotics. Complexes (1)-(4) revealed that they were not cytotoxic to HCT-8 cells. They also proved to interfere with the cellular cycle of tumour HCT-8 cells by increasing the number of cells found in the S and G2/M phases. Taken together, these results demonstrate the potential of zinc and copper complexes for use in the development of novel antimicrobial and anti-proliferative agents.

Development and Sequential Analysis of a New Multi-Agent, Anti-Acne Formulation Based on Plant-Derived Antimicrobial and Anti-Inflammatory Compounds.

The antibacterial and anti-inflammatory potential of natural, plant-derived compounds has been reported in many studies. Emerging evidence indicates that plant-derived essential oils and/or their major compounds may represent a plausible alternative treatment for acne, a prevalent skin disorder in both adolescent and adult populations. Therefore, the purpose of this study was to develop and subsequently analyze the antimicrobial activity of a new multi-agent, synergic formulation based on plant-derived antimicrobial compounds (i.e., eugenol, ß-pinene, eucalyptol, and limonene) and anti-inflammatory agents for potential use in the topical treatment of acne and other skin infections. The optimal antimicrobial combinations selected in this study were eugenol/ß-pinene/salicylic acid and eugenol/ß-pinene/2-phenoxyethanol/potassium sorbate. The possible mechanisms of action revealed by flow cytometry were cellular permeabilization and inhibition of efflux pumps activity induced by concentrations corresponding to sub-minimal inhibitory (sub-MIC) values. The most active antimicrobial combination represented by salycilic acid/eugenol/ß-pinene/2-phenoxyethanol/potassium sorbate was included in a cream base, which demonstrated thermodynamic stability and optimum microbiological characteristics.

Synthesis, Physico-chemical Characterization, Crystal Structure and Influence on Microbial and Tumor Cells of Some Co(II) Complexes with 5,7-Dimethyl-1,2,4-triazolo[1,5-a]pyrimidine.

Three complexes, namely [Co(dmtp)2(OH2)4][CoCl4] (1), [Co(dmtp)2Cl2] (2) and [Co(dmtp)2(OH2)4]Cl2∙2H2O (3) (dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine), were synthesized and characterized by spectral (IR, UV-Vis-NIR), and magnetic measurements at room temperature, as well as single crystal X-ray diffraction. Complex (1) crystallizes in monoclinic system (space group C2/c), complex (2) adopts an orthorhombic system (space group Pbca), and complex (3) crystallizes in triclinic system (space group P1). Various types of extended hydrogen bonds and π-π interactions provide a supramolecular architecture for all complexes. All species were evaluated for antimicrobial activity towards planktonic and biofilm-embedded microbial cells and influence on HEp-2 cell viability, cellular cycle and gene expression.

Gamma Radiation-Mediated Synthesis of Antimicrobial Polyurethane Foam/Silver Nanoparticles.

Nosocomial infections represent a major threat within healthcare systems worldwide, underscoring the critical need for materials with antimicrobial properties. This study presents the development of polyurethane foam embedded with silver nanoparticles (PUF/AgNPs) using a rapid, eco-friendly, in situ radiochemical synthesis method. The nanocomposites were characterized by UV-vis and FTIR spectroscopy, scanning electron microscopy coupled with energy dispersive X-ray technique (SEM/EDX), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), tensile and compression strengths, antimicrobial activity, and foam toxicity tests. The resulting PUF/AgNPs demonstrated prolonged stability (over 12 months) and good dispersion of AgNPs. Also, the samples presented higher levels of hardness compared to samples without AgNPs (deformation of 1682 µm for V1 vs. 4307 µm for V0, under a 5 N force), tensile and compression strength of 1.80 MPa and 0.34 Mpa, respectively. Importantly, they exhibited potent antimicrobial activity against a broad range of bacteria (including Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis) and a fungal mixture (no fungal growth on the sample surface was observed after 28 days of exposure). Furthermore, these materials were non-toxic to human keratinocytes, which kept their specific morphology after 24 h of incubation, highlighting their potential for safe use in biomedical applications. We envision promising applications for PUF/AgNPs in hospital bed mattresses and antimicrobial mats, offering a practical strategy to reduce nosocomial infections and enhance patient safety within healthcare facilities.

Phenotypic profiles of virulence in different Candida species isolated from vulvovaginal infections.

In order to establish an infection, pathogenic microorganisms have to colonize, survive, multiply, evade the immune system and spread to other tissues [1, 2, 3]. Although some Candida species are normally commensal in humans, in the last decades the frequency and the severity of nosocomial diseases due to Candida strains have increased dramatically [4]. The aim of the present study was to characterize some Candida strains isolated from vulvovaginal infections by determining the virulence and pathogenicity profile. The assessment of the in vitro expression of virulence cell wall associated factors (hyphal formation, adherence to HeLa cell line, biofilm development), soluble secreted enzymes (aspartyl protease, lipase, phospholipase, DN-ase) and Fe3+ accumulation was achieved by phenotypic methods on 13 yeast strains belonging to five Candida (C.) species (C. albicans, C. krusei, C. parapsilopsis, C. catenulata and C. kefyr). Candida sp. strains isolated from vulvovaginal infections showed species/ strain specific virulence profile.

Current and Future Flow Cytometry Applications Contributing to Antimicrobial Resistance Control.

Antimicrobial resistance is a global threat to human health and welfare, food safety, and environmental health. The rapid detection and quantification of antimicrobial resistance are important for both infectious disease control and public health threat assessment. Technologies such as flow cytometry can provide clinicians with the early information, they need for appropriate antibiotic treatment. At the same time, cytometry platforms facilitate the measurement of antibiotic-resistant bacteria in environments impacted by human activities, enabling assessment of their impact on watersheds and soils. This review focuses on the latest applications of flow cytometry for the detection of pathogens and antibiotic-resistant bacteria in both clinical and environmental samples. Novel antimicrobial susceptibility testing frameworks embedding flow cytometry assays can contribute to the implementation of global antimicrobial resistance surveillance systems that are needed for science-based decisions and actions.

Biological Evaluation and Structural Analysis of Some Aminodiphenylamine Derivatives.

4-Aminodiphenylamino derivatives were investigated for their antioxidant and hydrophobicity character, together with other biological measurements, such as antimicrobial and antibiofilm activity. Among these nine compounds used, we obtained novel derivatives via reaction of the starting material with NBD-chloride. Therefore, we performed a full structural analysis for these compounds, i.e., elemental analysis, IR, UV-Vis, 1H- and 13C-NMR, ESI-MS, X-ray diffraction on single crystal, etc. The hydrophobicity of all the compounds was measured either experimentally using the RP-TLC technique, or via calculation using the fragments method. The other structural characteristics were analyzed, and a correlation between the experimental and computed properties was found. Moreover, the results of the biological evaluation showed that some of the synthesized compounds have antimicrobial and antibiofilm activity.

Wastewater treatment plants, an "escape gate" for ESCAPE pathogens.

Antibiotics are an essential tool of modern medicine, contributing to significantly decreasing mortality and morbidity rates from infectious diseases. However, persistent misuse of these drugs has accelerated the evolution of antibiotic resistance, negatively impacting clinical practice. The environment contributes to both the evolution and transmission of resistance. From all anthropically polluted aquatic environments, wastewater treatment plants (WWTPs) are probably the main reservoirs of resistant pathogens. They should be regarded as critical control points for preventing or reducing the release of antibiotics, antibiotic-resistant bacteria (ARB), and antibiotic-resistance genes (ARGs) into the natural environment. This review focuses on the fate of the pathogens Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae spp. (ESCAPE) in WWTPs. All ESCAPE pathogen species, including high-risk clones and resistance determinants to last-resort antibiotics such as carbapenems, colistin, and multi-drug resistance platforms, were detected in wastewater. The whole genome sequencing studies demonstrate the clonal relationships and dissemination of Gram-negative ESCAPE species into the wastewater via hospital effluents and the enrichment of virulence and resistance determinants of S. aureus and enterococci in WWTPs. Therefore, the efficiency of different wastewater treatment processes regarding the removal of clinically relevant ARB species and ARGs, as well as the influence of water quality factors on their performance, should be explored and monitored, along with the development of more effective treatments and appropriate indicators (ESCAPE bacteria and/or ARGs). This knowledge will allow the development of quality standards for point sources and effluents to consolidate the WWTP barrier role against the environmental and public health AR threats.

Snapshot of the pollution-driven metabolic and microbiota changes in Carassius gibelio from Bucharest leisure lakes.

In the last decades, increased intakes of contaminants and the habitats' destruction have produced drastic changes in the aquatic ecosystems. The environmental contaminants can accumulate in aquatic organisms, leading to the disturbance of the antioxidant/prooxidant balance in fish. In this context, we evaluated the level of organic, inorganic and microbiological pollutants in four leisure lakes (Chitila, Floreasca, Tei and Vacaresti) from Bucharest, the largest city of Romania, in order to compare their effects on hepatopancreas and gills metabolism and antioxidant defense mechanisms in Carassius gibelio, the most known and widespread freshwater fish in this country. The lowest level of oxidative stress was recorded in the case of fish collected from the Vacaresti lake, a protected wetland area where aquatic organisms live in wild environmental conditions. In contrast, significant oxidative changes were observed in the hepatopancreas and gills of fish from the Chitila, Floreasca and Tei lakes, such as reduced glutathione S-transferase activity and glutathione level, and increased degree of lipid peroxidation, being correlated with elevated levels of pesticides (such as 2,4'-methoxychlor) and Escherichia coli load in these organs. Although different patterns of pollutants' accumulation were observed, no important interindividual variations in cytosine methylation degree were determined. In conclusion, the presence and concentrations of metals, pesticides and antibiotics varied with the analyzed tissue and sampling site, and were correlated with changes in the cellular redox homeostasis, but without significantly affecting the epigenetic mechanisms.

Macrophage-targeted mannose-decorated PLGA-vegetable oil hybrid nanoparticles loaded with anti-inflammatory agents.

This work pledge to extend the therapeutic windows of hybrid nanoparticulate systems by engineering mannose-decorated hybrid nanoparticles based on poly lactic-co-glycolic acid (PLGA) and vegetable oil for efficient delivery of two lipophilic anti-inflammatory therapeutics (Celecoxib-CL and Indomethacin-IMC) to macrophages. The mannose surface modification of nanoparticles is achieved via O-palmitoyl-mannose spacer during the emulsification and nanoparticles assembly process. The impact of targeting motif on the hydrodynamic features (RH, PdI), stability (ζ-potential), drug encapsulation efficiency (DEE) is thoroughly investigated. Besides, the in vitro biocompatibility (MTT, LDH) and susceptibility of mannose-decorated formulations to macrophage as well their immunomodulatory activity (ELISA) are also evaluated. The monomodal distributed mannose-decorated nanoparticles are in the range of nanometric size (RH < 115 nm) with PdI < 0.20 and good encapsulation efficiency (DEE = 46.15% for CL and 76.20% for IMC). The quantitative investigation of macrophage uptake shows a 2-fold increase in fluorescence (RFU) of cells treated with mannose-decorated formulations as compared to non-decorated ones (p < 0.001) suggesting an enhanced cell uptake respectively improved macrophage targeting while the results of ELISA experiments suggest the potential immunomodulatory properties of the designed mannose-decorated hybrid formulations.