Codetermination of antimicrobial agents in rabbit tear fluid using LC-MS/MS assay: Insights into ocular pharmacokinetic study.

Managing ocular microbial infections typically requires pharmacotherapy using antibiotic eye drops, such as moxifloxacin hydrochloride (MFX), combined with an antifungal agent like amphotericin B (AB). We carried out and validated an LC-MS/MS assay to quantify these compounds in rabbit tear fluid in order to look into the pharmacokinetics of these two drugs. We employed a protein precipitation technique for the extraction of drugs under examination. A Waters Symmetry C18 column was used to separate the analytes and internal standard. The composition of the mobile phase was like (A) 0.1% v/v formic acid in water and (B) methanol. The detection of MFX and AB was accomplished through the utilization of positive ion electrospray ionization under multiple reaction monitoring mode. The linearity curves for both analytes exhibited an acceptable trendline across a concentration range of 2.34-300 ng/mL for MFX and 7.81-1000 ng/mL for AB in surrogate rabbit tear fluid. The lower limit of quantitation for MFX was 2.34 ng/mL, while for AB, it was 7.81 ng/mL. The approach was strictly validated, encompassing tests of selectivity, linearity (with r2 > 0.99), precision, accuracy, matrix effects, and stability. Consequently, we employed this method to evaluate the pharmacokinetics profiles of MFX and AB in rabbit tear fluid following single topical doses.

Enantioselective synthesis, characterization, molecular docking simulation and ADMET profiling of α-alkylated carbonyl compounds as antimicrobial agents.

All living organisms produce only one enantiomer, so we found that all natural compounds are presented in enantiomerically pure form. Asymmetric synthesis is highly spread in medicinal chemistry because enantiomerically pure drugs are highly applicable. This study initially demonstrated the feasibility of a good idea for the asymmetric synthesis of α-alkylated carbonyl compounds with high enantiomeric purity ranging from 91 to 94% using different quinazolinone derivatives. The structure of all compounds was confirmed via elemental analysis and different spectroscopic data and the enantioselectivity was determined via HPLC using silica gel column. The synthesized compounds' mode of action was investigated using molecular docking against the outer membrane protein A (OMPA) and exo-1,3-beta-glucanase, with interpreting their pharmacokinetics aspects. The results of the antimicrobial effectiveness of these compounds revealed that compound 6a has a broad biocidal activity and this in-vitro study was in line with the in-silico results. Overall, the formulated compound 6a can be employed as antimicrobial agent without any toxicity with high bioavailability in medical applications.

Updated antimicrobial dosing recommendations for obese patients.

The prevalence of obesity has increased considerably in the last few decades. Pathophysiological changes in obese patients lead to pharmacokinetic (PK) and pharmacodynamic (PD) alterations that can condition the correct exposure to antimicrobials if standard dosages are used. Inadequate dosing in obese patients can lead to toxicity or therapeutic failure. In recent years, additional antimicrobial PK/PD data, extended infusion strategies, and studies in critically ill patients have made it possible to obtain data to provide a better dosage in obese patients. Despite this, it is usually difficult to find information on drug dosing in this population, which is sometimes contradictory. This is a comprehensive review of the dosing of different types of antimicrobials (antibiotics, antifungals, antivirals, and antituberculosis drugs) in obese patients, where the literature on PK and possible dosing strategies in obese adults was critically assessed.

The disposition of trimethoprim and sulfadiazine in neonatal foals after intravenous administration.

BACKGROUND: Septicaemia in the neonatal foal is caused by both Gram positive and Gram negative bacteria. The life-threatening nature of this condition requires treatment to be initiated with broad spectrum antimicrobial drugs pending antimicrobial susceptibility testing. Potentiated sulphonamides, for example, trimethoprim combined with sulfadiazine, could be clinically relevant options but their pharmacokinetics in the neonatal foal are unknown. OBJECTIVES: To describe the plasma disposition of trimethoprim and sulfadiazine in neonatal foals and to relate the results to patterns in the minimum inhibitory concentration (MIC) for Escherichia coli, a recognized pathogen in neonatal foal sepsis. METHOD: A total of five doses of trimethoprim (2.5 mg/kg) and sulfadiazine (12.5 mg/kg) were administered intravenously every 12 h to eight neonatal foals that were 3 days old at inclusion. A non-linear mixed effects model was fitted to the trimethoprim and sulfadiazine experimental data. The 24 h area under the free plasma trimethoprim and sulfadiazine concentration-time curves (fAUC) and the pharmacokinetic/pharmacodynamik (PK/PD)-index fAUC/MIC was calculated to evaluate the potential clinical benefits of the administered dose. RESULTS: For trimethoprim, the typical values were 1.99 L/kg, 0.33 L/h·kg and 4.2 h for the apparent volume of distribution, clearance and terminal half-life, respectively. The 24 h fAUC for trimethoprim was 11.3 µg·h/ml (7.2-15.2) and the fAUC/MIC ratio for E. coli was 23 (16.4-29.2) (population mean (range)). For sulfadiazine, the typical values were 0.61 L/kg, 0.09 L/h·kg and 5.3 h for the apparent volume of distribution, clearance and terminal half-life, respectively. The 24 h fAUC for sulfadiazine was 246.8 µg·h/ml (175.6-335.4). CONCLUSION: For trimethoprim, the plasma exposure is insufficient in some foals to successfully treat bacterial infections with an MIC-value of 0.5 µg/ml using the studied dosing regimen.

Impact of local and systemic antimicrobials on leukocyte- and platelet rich fibrin: an in vitro study.

The aim of this study was to evaluate the effect of local and systemic administration of antimicrobials to leukocyte- and platelet-rich fibrin (L-PRF). For part A, 16 tubes of venous blood were collected from each of eight systemically healthy subjects. Prior to blood centrifugation, 12 of the 16 tubes were injected with 0.125 ml, 0.25 ml or 0.50 ml metronidazole solution. One set of L-PRF membranes was used to assess the release of vascular endothelial growth factor AB, platelet-derived growth factor, transforming growth factor beta 1, and bone morphogenetic protein 2 at indicated time points. The metronidazole release over time by L-PRF membranes was also evaluated. The remaining L-PRF membranes were placed on the surface of agar plates inoculated with three different periodontal pathogens to determine their antibacterial activity. For part B, another six subjects were enrolled with three subjects taking 2 g amoxicillin and three subjects 500 mg metronidazole as prophylaxis prior to a periodontal treatment. Before and 2 h after consuming one of the prescribed antimicrobials, three tubes of blood were collected for preparing L-PRF membranes. These membranes were used to measure the antibacterial activity against periodontal pathogens. No statistically significant difference could be found in the release of growth factors between L-PRF membranes with and without incorporation of metronidazole solution. The release of metronidazole could be detected up to day 3, however with the highest concentration during the first 4 h. This concentration was dose dependent. The antibacterial capacity of L-PRF membranes increased significantly for both the systemic intake, and after the addition of metronidazole solution to the blood tubes before centrifugation, the latter again dose dependent. The antibacterial capacity of L-PRF against the periodontal pathogens tested can significantly be enhanced by the addition of antimicrobials, without disadvantage for the release of growth factors.

Modeling bioaffinity-based targeted delivery of antimicrobials to Escherichia coli biofilms using yeast microparticles. Part II: Parameter evaluation and validation.

The design of bioaffinity-based targeted delivery systems for biofilm inactivation may require a comprehensive understanding of physicochemical and biochemical properties of biobased antimicrobial particles and their interactions with biofilm. In this study, Escherichia coli biofilm inactivation by chlorine-charged yeast microparticles was numerically simulated, and the roles of chemical stability, binding affinity, and controlled release of this targeted delivery system were assessed using this numerical simulation. The simulation results were experimentally validated using two different types of yeast microparticles. The results of this study illustrate that chorine stability achieved by yeast microparticles was a key factor for improved biofilm inactivation in an organic-rich environment (>6 additional log reduction in 20 min compared to the free chlorine treatment). Moreover, the binding affinity of yeast microparticles to E. coli biofilms was another key factor for an enhanced inactivation of biofilm, as a 10-fold increase in binding rate resulted in a 4.2-fold faster inactivation. Overall, the mechanistic modeling framework developed in this study could guide the design and development of biobased particles for targeted inactivation of biofilms.

Health Benefits and Pharmacological Properties of Carvone.

Carvone is a monoterpene ketone contained in the essential oils of several aromatic and medicinal plants of the Lamiaceae and Asteraceae families. From aromatic plants, this monoterpene is secreted at different concentrations depending on the species, the parts used, and the extraction methods. Currently, pharmacological investigations showed that carvone exhibits multiple pharmacological properties such as antibacterial, antifungal, antiparasitic, antineuraminidase, antioxidant, anti-inflammatory, and anticancer activities. These studies were carried out in vitro and in vivo and involved a great deal of knowledge on the mechanisms of action. Indeed, the antimicrobial effects are related to the action of carvone on the cell membrane and to ultrastructural changes, while the anti-inflammatory, antidiabetic, and anticancer effects involve the action on cellular and molecular targets such as inducing of apoptosis, autophagy, and senescence. With its multiple mechanisms, carvone can be considered as natural compounds to develop therapeutic drugs. However, other investigations regarding its precise mechanisms of action as well as its acute and chronic toxicities are needed to validate its applications. Therefore, this review discusses the principal studies investigating the pharmacological properties of carvone, and the mechanism of action underlying some of these properties. Moreover, further investigations of major pharmacodynamic and pharmacokinetic studies were also suggested.

Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl ß-D-Galactopyranoside Analogs.

A series of methyl ß-D-galactopyranoside (MGP, 1) analogs were selectively acylated with cinnamoyl chloride in anhydrous N,N-dimethylformamide/triethylamine to yield 6-O-substitution products, which was subsequently converted into 2,3,4-tri-O-acyl analogs with different acyl halides. Analysis of the physicochemical, elemental, and spectroscopic data of these analogs revealed their chemical structures. In vitro antimicrobial testing against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) showed promising antifungal functionality comparing to their antibacterial activities. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests were conducted for four compounds (4, 5, 6, and 9) based on their activity. MTT assay showed low antiproliferative activity of compound 9 against Ehrlich's ascites carcinoma (EAC) cells with an IC50 value of 2961.06 µg/mL. Density functional theory (DFT) was used to calculate the thermodynamic and physicochemical properties whereas molecular docking identified potential inhibitors of the SARS-CoV-2 main protease (6Y84). A 150-ns molecular dynamics simulation study revealed the stable conformation and binding patterns in a stimulating environment. In-silico ADMET study suggested all the designed molecules to be non-carcinogenic, with low aquatic and non-aquatic toxicity. In summary, all these antimicrobial, anticancer and in silico studies revealed that newly synthesized MGP analogs possess promising antiviral activity, to serve as a therapeutic target for COVID-19.

Regulatory utility of pharmacometrics in the development and evaluation of antimicrobial agents and its recent progress in China.

Pharmacometrics is an emerging science that interprets drug, disease, and trial information in a mathematical fashion to inform and facilitate efficient drug development and/or regulatory decisions. Pharmacometrics study is increasingly adopted in the regulatory review of new antimicrobial agents. We summarized the 31 antimicrobial agents approved by the US Food and Drug Administration (FDA) and the 26 antimicrobial agents approved by European Medicines Agency (EMA) from January 2001 to May 2019. We also reviewed recent examples of utilizing pharmacometrics to support antimicrobial agent's registration in China, including modeling and simulation methods, effects of internal/external factors on pharmacokinetic (PK) parameters, safety and efficacy evaluation in terms of exposure-response analysis, refinement of the wording of product labeling and package leaflet, and possible postmarketing clinical trial. Ongoing communication among regulator, academia, and industry regarding pharmacometrics is encouraged to streamline and facilitate the development of new antimicrobial agents. The industry can maximize its benefit in drug development through continued pharmacometrics education/training.

Proceedings of Chemistry, Pharmacology, Pharmacokinetics and Synthesis of Biflavonoids.

Biflavonoids, composed of two monoflavonoid residues, occur naturally in angiosperms, bryophytes, ferns, and gymnosperms. More than 592 biflavonoids have been structurally elucidated, and they can be classified into two groups of C-C and C-linear fragments-C, based on whether the linker between the two residues contains an atom. As the linker can be established on two arbitrary rings from different residues, the C-C type contains various subtypes, as does the C-linear fragment-C type. Biflavonoids have a wide range of pharmacological activities, including anti-inflammatory, antioxidant, antibacterial, antiviral, antidiabetic, antitumor, and cytotoxic properties, and they can be applied in Alzheimer's disease and Parkinson's disease. This review mainly summarizes the distribution and chemistry of biflavonoids; additionally, their bioactivities, pharmacokinetics, and synthesis are discussed.

Metabolism is not a Major Contributor to the Toxicity of Piperaquine, a Long-acting Antimalarial Agent in Artemisinin-based Combination Therapy.

BACKGROUND: Hepatocellular damage has been reported for the antimalarial piperaquine (PQ) in the clinic after cumulative doses. OBJECTIVES: The role of metabolism in PQ toxicity was evaluated, and the mechanism mediating PQ hepatotoxicity was investigated. METHODS: The toxicity of PQ and its major metabolite (PQ N-oxide; M1) in mice was evaluated in terms of serum biochemical parameters. The role of metabolism in PQ toxicity was investigated in mice pretreated with an inhibitor of CYP450 (ABT) and/or FMO enzyme (MMI). The dose-dependent pharmacokinetics of PQ and M1 were studied in mice. Histopathological examination was performed to reveal the mechanism mediating PQ hepatotoxicity. RESULTS: Serum biochemical levels (ALT and BUN) increased significantly (P < 0.05) in mice after three-day oral doses of PQ (> 200 mg/kg/day), indicating hepatotoxicity and nephrotoxicity of PQ at a high dose. Weaker toxicity was observed for M1. Pretreatment with ABT and/or MMI did not increase PQ toxicity. PQ and M1 showed linear pharmacokinetics in mice after a single oral dose, and multiple oral doses led to their cumulative exposures. Histopathological examination showed that a high dose of PQ (> 200 mg/kg/day for three days) could induce hepatocyte apoptosis. The mRNA levels of targets in NF-κB and p53 pathways could be up-regulated by 2-30-fold in mice by PQ or M1. CONCLUSION: PQ metabolism led to detoxification of PQ, but there was a low possibility of altered toxicity induced by metabolism inhibition. The hepatotoxicity of PQ and its N-oxidation metabolite was partly mediated by NF-κB inflammatory pathway and p53 apoptosis pathway.

Development of N,O-Carboxymethyl Chitosan-Starch Biomaterial Inks for 3D Printed Wound Dressing Applications.

In this paper, a novel hybrid biomaterial ink consisting of two water-soluble polymers is investigated: starch and N,O-carboxymethyl chitosan (NOCC). The biomaterial ink is used to fabricate controlled release biodegradable wound dressing scaffolds via a novel low-temperature solvent (organic)-free 3D printing technique. NOCC is a variant of chitosan with a high degradation rate that can lead to an immediate release of the drugs, and starch, on the other hand, is used to alter degradation and drug release characteristics of the biomaterial. Mupirocin, a topical anti-infective, is incorporated into the biomaterial inks. Different biomaterial inks in terms of NOCC to starch ratio are prepared and characterized. Printability and rheology of the samples are investigated, and the release of mupirocin over time is quantified. The efficacy of the developed 3D printed wound dressings against Staphylococcus aureus is examined through disk diffusion assays. Increasing NOCC accelerated the release of the drug from the scaffold and led to larger zones of inhibition in the early hours of the in vitro tests; this phenomenon is correlated to the enhanced hydrophilicity of NOCC-dominated scaffolds. The drug release and the zone of inhibition are controlled by altering starch to NOCC ratio in the biomaterial ink.

Determination of polyphenols and in vitro antimicrobial and antioxidant activity of Calluna vulgaris (L.) Hull.

Calluna vulgaris (L.) Hull belonging to Ericaceae family occurs mostly at sour habitats in subalpine regions in Europe. The species is cultivated in many countries, but it is known as medicinal plant because of polyphenols and aucubin as main compounds. In this work, the polyphenolic, flavonoid, and tannin content, as well as the antimicrobial and antioxidant activity of the aerial part, were evaluated. In phytochemical analyses, methanol extract showed the highest phenolic and flavonoid content, followed by ethanol, methanol/water, and aqueous extracts. In antimicrobial tests, chloroform, ethyl acetate, butanol, and water extracts inhibited the growth of S. aureus and MRSA, while butanol and water fractions were effective against E. coli, and water extract for E. coli ESBL and K. pneumoniae ESBL. Water extract showed the most inhibitory effect for the tested 2 g-positive and 3 g-negative strains including both bactericidal and bacteriostatic activity. Data analysed by Pearson coefficient correlation showed positive correlation between polyphenol and flavonoid content. The determined antioxidant capacity of the herb ranged from 0.145 to 0.296 mg/mL. The results highlight the significance of the plant as possible antioxidant source and as an antimicrobial agent for further studies.

Oxazinethione Derivatives as a Precursor to Pyrazolone and Pyrimidine Derivatives: Synthesis, Biological Activities, Molecular Modeling, ADME, and Molecular Dynamics Studies.

In this study, we used oxazinethione as a perfect precursor to synthesize new pyrimidine and pyrazole derivatives with potent biological activities. Biological activities were determined for all compounds against A. flavus, E. coli, S. aureus, and F. moniliform. Compounds 3, 4a-b, and 5 exhibited higher activities toward A. flavus, E. coli, S. aureus, and F. moniliform; this was indicated through the MIC (minimum inhibitory concentration). At the same time, anticancer activities were determined through four cell lines, Ovcar-3, Hela, MCF-7, and LCC-MMk. The results obtained indicated that compound 5 was the most potent compound for both cell lines. Molecular docking was studied by the MOE (molecular operating environment). The in silico ADME of compounds 2 and 5 showed good pharmacokinetic properties. The present research strengthens the applicability of these compounds as encouraging anticancer and antibacterial drugs. Moreover, JAGUAR module MD simulations were carried out at about 100 ns. In addition, spectroscopic studies were carried out to establish the reactions of the synthesized structure derivatives.

In-Vivo Analysis and Model-Based Prediction of Tensides' Influence on Drug Absorption.

Depending on their concentrations the surface-active substances, tensides (surfactants) can positively or negatively influence the drug absorption, which is widely used in the design of the dosage forms with controlled release. A problem is that the (in-vivo) rate of absorption cannot be directly measured and for that reason, it is frequently substituted by evaluation of the (in-vitro) dissolution. On other hand, a suitably designed pharmacokinetic model can directly predict virtually all pharmacokinetic quantities including both the rate of absorption and fraction of the dose reaching the blood circulation. The paper presents a new approach to the analysis of the rate of drug absorption and shows its superiority over traditional in-vivo approaches. Both the in-vivo analysis and model-based prediction of the tenside (monolaurin of sucrose) influence on the rate of absorption of the drug (sulfathiazole) after instantaneous per-oral administration to rats are discussed. It was found that 0.001% solution of tenside can increase the rate of absorption by cca 50% and a two-fold increase in absolute bioavailability can be reached. Attention is also devoted to the formal requirements laid on the model's structure and its identifiability. The systematic design, substantiation and validation of a parsimonious predictive model that confirms in-vivo results are presented. The match between in-vivo observations and model-based predictions is demonstrated. The frequently overlooked metaphysics lying behind the compartmental modelling is briefly explained.

Visualizing and quantifying antimicrobial drug distribution in tissue.

The biodistribution and pharmacokinetics of drugs are vital to the mechanistic understanding of their efficacy. Measuring antimicrobial drug efficacy has been challenging as plasma drug concentration is used as a surrogate for tissue drug concentration, yet typically does not reflect that at the intended site(s) of action. Utilizing an image-guided approach, it is feasible to accurately quantify the biodistribution and pharmacokinetics within the desired site(s) of action. We outline imaging modalities used in visualizing drug distribution with examples ranging from in vitro cellular drug uptake to clinical treatment of microbial infections. The imaging modalities of interest are: radio-labeling, magnetic resonance, mass spectrometry imaging, computed tomography, fluorescence, and Raman spectroscopy. We outline the progress, limitations, and future outlook for each methodology. Further advances in these optical approaches would benefit patients and researchers alike, as non-invasive imaging could yield more profound insights with a lower clinical burden than invasive measurement approaches used today.

Pharmacokinetics of Commonly Used Antimicrobials in Critically Ill Adults During Extracorporeal Membrane Oxygenation: A Systematic Review.

PURPOSE: Adequate dosing of antimicrobials is critical to properly treat infections and limit development of resistance and adverse effects. Limited guidance exists for antimicrobial dosing adjustments in patients requiring extracorporporeal membrane oxygenation (ECMO) therapy. A systematic review was conducted to delineate the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in critically ill adult patients requiring ECMO. METHODS: Medline, EMBASE, Global Health, and All EBM Reviews databases were searched. Grey literature was examined. All studies reporting PK/PD parameters of antimicrobials in critically ill adults treated with ECMO were included, except for case reports and congress abstracts. Ex vivo studies were included. Two independent reviewers applied the inclusion and exclusion criteria. Reviewers were then paired to independently abstract data and evaluate methodological quality of studies using the ROBINS-I tool and the compliance with ClinPK guidelines. Patients' and studies' characteristics, key PK/PD findings, details of ECMO circuits and co-treatments were summarized qualitatively. Dosing recommendations were formulated based on data from controlled studies. RESULTS: Thirty-two clinical studies were included; most were observational and uncontrolled. Fourteen ex vivo studies were analysed. Information on patient characteristics and co-treatments was often missing. The effect of ECMO on PK/PD parameters of antimicrobials varied depending on the studied drugs. Few dosing recommendations could be formulated given the lack of good quality data. CONCLUSION: Limited data exist on the PK/PD of antimicrobials during ECMO therapy. Rigorously designed and well powered populational PK studies are required to establish empiric dosing guidelines for antimicrobials in patients requiring ECMO support. PROSPERO REGISTRATION NUMBER: CRD42018099992 (Registered: July 24th 2018).

Individualized precision dosing approaches to optimize antimicrobial therapy in pediatric populations.

INTRODUCTION: Severe infections continue to impose a major burden on critically ill children and mortality rates remain stagnant. Outcomes rely on accurate and timely delivery of antimicrobials achieving target concentrations in infected tissue. Yet, developmental aspects, disease-related variables, and host factors may severely alter antimicrobial pharmacokinetics in pediatrics. The emergence of antimicrobial resistance increases the need for improved treatment approaches. AREAS COVERED: This narrative review explores why optimization of antimicrobial therapy in neonates, infants, children, and adolescents is crucial and summarizes the possible dosing approaches to achieve antimicrobial individualization. Finally, we outline a roadmap toward scientific evidence informing the development and implementation of precision antimicrobial dosing in critically ill children.The literature search was conducted on PubMed using the following keywords: neonate, infant, child, adolescent, pediatrics, antimicrobial, pharmacokinetic, pharmacodynamic target, Bayes dosing software, optimizing, individualizing, personalizing, precision dosing, drug monitoring, validation, attainment, and software implementation. Further articles were sought from the references of the above searched articles. EXPERT OPINION: Recently, technological innovations have emerged that enabled the development of individualized antimicrobial dosing approaches in adults. More work is required in pediatrics to make individualized antimicrobial dosing approaches widely operationalized in this population.

Enhancement of Biological and Pharmacological Properties of an Encapsulated Polyphenol: Curcumin.

There is a dearth of natural remedies available for the treatment of an increasing number of diseases facing mankind. Natural products may provide an opportunity to produce formulations and therapeutic solutions to address this shortage. Curcumin (CUR), diferuloylmethane; I,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione is the major pigment in turmeric powder which has been reported to exhibit a number of health benefits including, antibacterial, antiviral, anti-cancer, anti-inflammatory and anti-oxidant properties. In this review, the authors attempt to highlight the biological and pharmacological properties of CUR in addition to emphasizing aspects relating to the biosynthesis, encapsulation and therapeutic effects of the compound. The information contained in this review was generated by considering published information in which evidence of enhanced biological and pharmacological properties of nano-encapsulated CUR was reported. CUR has contributed to a significant improvement in melanoma, breast, lung, gastro-intestinal, and genito-urinary cancer therapy. We highlight the impact of nano-encapsulated CUR for efficient inhibition of cell proliferation, even at low concentrations compared to the free CUR when considering anti-proliferation. Furthermore nano-encapsulated CUR exhibited bioactive properties, exerted cytotoxic and anti-oxidant effects by acting on endogenous and cholinergic anti-oxidant systems. CUR was reported to block Hepatitis C virus (HCV) entry into hepatic cells, inhibit MRSA proliferation, enhance wound healing and reduce bacterial load. Nano-encapsulated CUR has also shown bioactive properties when acting on antioxidant systems (endogenous and cholinergic). Future research is necessary and must focus on investigation of encapsulated CUR nano-particles in different models of human pathology.