In silico toxicity and immunological interactions of components of calcium silicate-based and epoxy resin-based endodontic sealers.

OBJECTIVES: The present study aimed to determine in silico toxicity predictions of test compounds from hydraulic calcium silicate-based sealers (HCSBS) and AH Plus and computationally simulate the interaction between these substances and mediators of periapical inflammation via molecular docking. MATERIALS AND METHODS: All chemical information of the test compounds was obtained from the PubChem site. Predictions for bioavailability and toxicity analyses were determined by the Molinspiration Cheminformatics, pkCSM, ProTox-II and OSIRIS Property Explorer platforms. Molecular docking was performed using the Autodock4 AMDock v.1.5.2 program to analyse interactions between proteins (IL-1ß, IL-6, IL-8, IL-10 and TNF-α) and ligands (calcium silicate hydrate, zirconium oxide, bisphenol-A epoxy resin, dibenzylamine, iron oxide and calcium tungstate) to establish the affinity and bonding mode between systems. RESULTS: Bisphenol-A epoxy resin had the lowest maximum dose tolerated in humans and was the test compound with the largest number of toxicological properties (hepatotoxicity, carcinogenicity and irritant). All systems had favourable molecular docking. However, the ligands bisphenol-A epoxy resin and dibenzylamine had the greatest affinity with the cytokines tested. CONCLUSION: In silico predictions and molecular docking pointed the higher toxicity and greater interaction with mediators of periapical inflammation of the main test compounds from AH Plus compared to those from HCSBS. CLINICAL RELEVANCE: This is the first in silico study involving endodontic materials and may serve as the basis for further research that can generate more data, producing knowledge on the interference of each chemical compound in the composition of different root canal sealers.

Chemical composition, antifungal activity, antibiofilm and citotoxicity of the essential oil of Citrus deliciosa tenore.

The leaves of Citrus deliciosa Tenore were collected in southern Brazil, dried, and subjected to the hydrodistillation process to obtain the essential oil. The extraction of essential oil yielded 0.97% ± 0.04. The chromatographic profile of this compound revealed 11 substances, being methyl N-methyl-anthranilate (75.1%), γ-terpinene (13.8%), and Limonene (7%) as major substances. The essential oil shows antifungal action against all tested yeasts, with promising action against Cryptococcus neoformans, Cryptococcus gattii, and Trichosporon asahii. This compound was also able to inhibit the biofilm production of Candida albicans, Candida glabrata, Candida parapsilosis, and T. asahii. The essential oil of tangerine showed weak antioxidant action. It did not show cytotoxicity in human mononuclear cells. It is hoped that these results may guide future studies for the production of formulations that can be used in the treatment of biofilms caused by yeasts, as well as in candidiasis, cryptococcosis, and/or trichosporonosis.

Impact of free curcumin and curcumin nanocapsules on viability and oxidative status of neural cell lines.

Curcumin is an active polyphenol substance found in the highest concentrations in the roots of Curcuma longa. Its health benefits have led to recent increases in the consumption of curcumin. It has anti-inflammatory and antioxidant activities and is a potent neuroprotective against diseases of the brain. Nevertheless, its low bioavailability and its relative difficulty crossing the blood-brain barrier limit curcumin's use for these purposes. Curcumin-loaded nanoparticles may be an effective treatment for several diseases although there is a paucity of studies reporting its safety in the central nervous system (CNS). Therefore, this study aimed to identify non-neurotoxic concentrations of free curcumin and two nanoformulations of curcumin. Cell lines BV-2 and SH-SY5Y, both originating from the CNS, were evaluated after 24, 48, and 72 h of treatment with free curcumin and nanocapsules We measured viability, proliferation, and dsDNA levels. We measured levels of reactive oxygen species and nitric oxide as proxies for oxidative stress in culture supernatants. We found that free curcumin was toxic at 10 and 20 µM, principally at 72 h. Nanoformulations were more neurotoxic than the free form. Safe concentrations of free curcumin are between 1-5 µM, and these concentrations were lower for nanoformulations. We determined the ideal concentrations of free curcumin and nanocapsules serving as a basis for studies of injuries that affect the CNS.

Eucalyptus oil nanoemulsions against eggs and larvae of Haemonchus contortus.

Haemonchus contortus is a highly pathogenic and prevalent helminth that causes many deaths in sheep herds. Anthelmintics are usually employed to overcome this issue; however, they do not guarantee immediate and lasting efficacy because of the occurrence of drug-resistant parasites. Among substances that are used in scientific studies for parasitic control, essential oils are known to have different pharmacological properties. However, they demonstrate instability owing to several factors, and therefore, nanoemulsification is considered an alternative to control the instability and degradability of these compounds. The objective of this study was to evaluate the cytotoxicity of nanoemulsions containing essential oil of Eucalyptus globulus against the blood of healthy sheep and to verify their activity against the parasite H. contortus in sheep. The results presented adequate nanotechnological characteristics (diameter 72 nm, PDI 0.2, zeta -11 mV, and acidic pH) and adequate morphology. Further, the corona effect and cytotoxic profiles of the free oil and nanoemulsion against blood cells from healthy sheep were evaluated. The tests results did not present a toxicity profile. For evaluating efficacy, we observed an important anthelmintic action of the nanoemulsion containing oil in comparison to the free oil; the results demonstrate a potential role of the nanoemulsion in the inhibition of egg hatchability and the development of larvae L1 to L3 (infective stage). Based on these results, we developed an important and potential anthelmintic alternative for the control of the parasite H. contortus.

Antimycobacterial activity of Achyrocline flaccida (Asteraceae) aqueous extract from Southern Brazil.

Achyrocline flaccida aqueous extract was obtained by macerating wildflowers. The phytochemical profile present in the A. flaccida aqueous extract was elucidated by HPLC-ESI-MS/MS. Toxicity was evaluated in vitro by comet assay in peripheral blood mononuclear cells (PBMCs) and in vivo using Caenorhabditis elegans as a model. The antioxidant activity was also evaluated, and antimycobacterial activity was assessed by the broth microdilution method. The compounds present in the aqueous extract mainly belonged to the flavonoid class (89%). The concentrations that showed protective effects in C. elegans against oxidative stress and antimycobacterial activity had no toxic effects. The antimycobacterial activity test demonstrated that the concentration of 1,560 µg mL-1 inhibited the growth and eradication of the mycobacterial tested strains. Based on our findings, the A. flaccida aqueous extract presents a viable potential in developing new phytotherapeutic drugs against mycobacteria of clinical relevance.

Phytochemical characterization, genotoxicity, cytotoxicity, and antimicrobial activity of Gautheria procumbens essential oil.

This study investigated the chemical constituents of Gaultheria procumbens essential oil and is the first to relate cytogenotoxicity with oxidative metabolism and antimicrobial activity. Chromatographic analysis of the essential oil showed methyl salicylate (99.96%) and linalool (0.04%) as the major compounds. The essential oil showed no signs of cytogenotoxicity at different concentrations (1.82 to 58.34 mg mL-1). Furthermore, G. procumbens essential oil and methyl salicylate were used to evaluate the minimal inhibitory concentrations (MIC) and minimal microbicidal concentrations (MMC). The results showed efficacy against several microorganisms, including Aeromonas caviae, Candida albicans, and Mycobacterium fortuitum with MIC values ranging from 1.82 to 3.64 mg mL-1 and MMC values ranging from 3.64 to 12.67 mg mL-1, which were confirmed by time-kill kinetics. Based on our results, the essential oil is a promising alternative to developing future formulations to treat infections caused by microorganisms.

Development, characterisation, stability study and antileukemic evaluation of nanoemulsions containing Astrocaryum aculeatum extract.

The objective of this work was to produce and characterise nanoemulsions containing tucumã extract and to evaluate the performance of the nanostructure and the free compound regarding antitumor activity, cytotoxicity, and oxidative metabolism in NB4/APL cells. The nanoemulsions showed adequate physicochemical characteristics (average size approx. 200 nm, polydispersity index less than 0.3, negative zeta potential and acid pH) maintained stable up to 90 days of storage in refrigeration condition. The nanoformulations did not present protein corona formation. Blank nanoemulsion treatments showed moderate toxicity. Furthermore, the nanoemulsion loaded with extract showed better antileukemic results than the free extract. However, nanoemulsions can be promising carriers of natural compounds, emphasising their biological properties and constituting alternatives in treating diseases.

Açaí (Euterpe oleracea Mart.) presents anti-neuroinflammatory capacity in LPS-activated microglia cells.

INTRODUCTION: Neuropsychiatric diseases are responsible for one of the highest burden of morbidity and mortality worldwide. These illnesses include schizophrenia, bipolar disorder, and major depression. Individuals affected by these diseases may present mitochondrial dysfunction and oxidative stress. Additionally, patients also have increased peripheral and neural chronic inflammation. The Brazilian fruit, açaí, has been demonstrated to be a neuroprotective agent through its recovery of mitochondrial complex I activity. This extract has previously shown anti-inflammatory effects in inflammatory cells. However, there is a lack of understanding of potential anti-neuroinflammatory mechanisms, such as cell cycle involvement. OBJECTIVE: The objective of this study is to evaluate the anti-neuroinflammatory potential of an açaí extract in lipopolysaccharide-activated BV-2 microglia cells. METHODS: Açaí extract was produced and characterized through high performance liquid chromatography. Following açaí extraction and characterization, BV-2 microglia cells were activated with LPS and a dose-response curve was generated to select the most effective açaí dose to reduce cellular proliferation. This dose was then used to assess reactive oxygen species (ROS) production, double-strand DNA release, cell cycle modulation, and cytokine and caspase protein expression. RESULTS: Characterization of the açaí extract revealed 10 bioactive molecules. The extract reduced cellular proliferation, ROS production, and reduced pro-inflammatory cytokines and caspase 1 protein expression under 1 µg/mL in LPS-activated BV-2 microglia cells but had no effect on double strand DNA release. Additionally, açaí treatment caused cell cycle arrest, specifically within synthesis and G2/Mitosis phases. CONCLUSION: These results suggest that the freeze-dried hydroalcoholic açaí extract presents high anti-neuroinflammatory potential.

Evaluation of the in vivo safety of tucumã oil nanocapsules in an experimental model of silver catfish Rhamdia quelen.

The aim of this study was to evaluate the toxicity of tucumã oil nanocapsules from the Amazon region in silver catfish, Rhamdia quelen. Fish were exposed to water treated with different concentrations of tucumã nanocapsules, white, solubilized oil and surfactant vehicles. After three days of exposure, fish were euthanized and liver, gills and brain removed for analysis of the dichlorofluorescein, nitric oxide and PicoGreen® assays. Plasma was collected for assay of hepatic transaminases. The nanocapsules had a diameter of 221 ± 1.27 nm, confirmed by atomic force microscopy. The oil nanocapsules were not toxic to this species of fish, but white nanocapsules and surfactant increased the levels of reactive oxygen species. Thus, nanocapsules are promising for the transport of tucumã oil. In view of the anti-inflammatory properties of this oil, it is possible to envisage its application in skin diseases for example, since they present essentially inflammatory conditions.HighlightsThe most abundant carotenoid in tucumã oil was all-trans-beta-carotene.Nanocapsules are good carriers for tucumã oil.Tucumã oil nanocapsules does nothas toxicity effect in catfish.

Ferulic acid-loaded nanocapsules: Evaluation of mucosal interaction, safety and antioxidant activity in human mononucleated cells.

Ferulic acid (FA) is a phenolic compound that has antioxidant, anti-inflammatory and anticarcinogenic properties besides presenting cytoprotective activity. It has limited oral bioavailability what is a challenge to its therapeutic application. In this way, this investigation aimed to develop FA-loaded nanocapsule suspensions (NC-FA) prepared with ethylcellulose and evaluate their in vitro release profile, mucoadhesion and irritation potential; scavenging capacity, cytotoxicity, cytoprotection and genoprotection against hydrogen peroxide-induced damage in hMNC (human Mononucleated Cells) culture. The nanocapsules presented physicochemical characteristics compatible with colloidal systems (NC-FA: 112 ± 3 nm; NC-B (without FA): 107 ± 3 nm; PdI < 0.2; Span<2.0 and negative zeta potential). In addition, the nanoparticulate system promoted the FA controlled release, increasing the half-life twice through the in vitro dialysis method. NC-FA and NC-B were able to interact with mucin, which is an indicative of mucoadhesive properties and the association of FA with nanocapsules showed decreased irritation by HET-CAM method. Besides, the NC-FA did not present cytotoxicity in hMNC and improved the ATBS radical scavenging capacity. Besides, it prevented, treated and reversed oxidative conditions in a H2O2-induced model in hMNC. Thus, this nanocarrier formulation is promising to perform more preclinical investigations focusing on diseases involving oxidative mechanisms.

Randia ferox (Cham & Schltdl) DC.: phytochemical composition, in vitro cyto- and genotoxicity analyses.

Randia ferox is a Brazilian native species used in folk medicine. Scientific information regarding the toxicology and phytochemistry of this plant remains unclear. We aimed to produce a R. ferox extract, identify its chemical matrix, and evaluate its safety profile. The extract chemical composition was accessed through UHPLC-MS/MS. Mononuclear cells, erythrocytes, fibroblasts, macrophages, and kidney cells were subjected to extract concentration-response curve testing. The cellular viability, proliferation, dsDNA release, reactive oxygen species (ROS), nitric oxide (NO), hemolysis, and DNA damage were determined. Ten molecules were found in the extract matrix. Most of the tested concentrations can be considered safe. Cellular viability, proliferation, dsDNA release, and NO remained at similar levels to the control. The extract increased ROS in macrophages. None of the tested concentrations induced DNA damage or hemolysis. The data suggest R. ferox extract contains several bioactive molecules and has a safety profile in vitro.

Parasporin A13-2 of Bacillus thuringiensis Isolates from the Papaloapan Region (Mexico) Induce a Cytotoxic Effect by Late Apoptosis against Breast Cancer Cells.

The protein A13-2 was obtained from Bacillus thuringiensis strains isolated from the Papaloapan watershed region (Oaxaca, Mexico). The cytotoxic activity of parasporal inclusions was studied against breast cancer cell line (MCF-7) and normal cell (human peripheral blood mononuclear cells). The MTT, the formation of reactive species, nitric oxide, free cell DNA, and the type of death cellular were assessed. The protein A13-2 shows the highest cytotoxic activity against MCF-7 (13% cell viability at 6 µg/mL), the extracellular DNA increases, and it shows no stress for reactive species or nitric oxide. Besides, the A13-2 parasporin shows no toxicity to peripheral blood mononuclear cells, and it does not generate changes in nitric oxide levels or free cell DNA. Due to that, the cytotoxic effect of A13-2 was specific for MCF-7, and it does not affect normal cells. According to microscopy and flow cytometry, A13-2 parasporin leads to the death of MCF-7 cells by late apoptosis together with necrosis and without allowing the triggering of the survival mechanisms. When analyzed together, our results show for the first time that the A13-2 protein isolated from Mexican strains of B. thuringiensis preferentially kills MCF- 7 (cancer cells) over HEK 293 and PBMC cell lines (normal cells), thus representing a promising alternative for the treatment of cancer breast.

Molecular docking, quorum quenching effect, antibiofilm activity and safety profile of silver-complexed sulfonamide on Pseudomonas aeruginosa.

Microbial infections caused by sessile microorganisms are known to be a more challenging issue than infections caused by the same microorganisms in the planktonic state. Pseudomonas aeruginosa is an opportunistic pathogen and biofilm-forming agent. This species presents intense cellular communication mediated by signaling molecules. This process is known as quorum sensing (QS) and induces the transcription of specific genes that favors cell density growth and three-dimensional bacterial grouping. In this context, the discovery of compounds capable of inhibiting the action of the QS signaling molecules seems to be a promising strategy against biofilms. This work aimed to evaluate the anti-biofilm action and the in vitro safety profile of a sulfamethoxazole-Ag complex. The results obtained indicate potential anti-biofilm activity through QS inhibition. In silico tests showed that the compound acts on the las and pqs systems, which are the main regulators of biofilm formation in P. aeruginosa. Additionally, the molecule proved to be safe for human peripheral blood mononuclear cells.

Phytochemical analysis and evaluation of the antioxidant and antiproliferative effects of Tucumã oil nanocapsules in breast adenocarcinoma cells (MCF-7).

In this work was to develop an inedited nanocapsule with tucumã oil (Astrocaryum vulgare). The oil presents of phytosterols (squalene and ß-sitosterol), all-trans-beta-carotene, acids oleic and palmitic. Antioxidant activity showed a good performance in DPPH and ABTS assays. The nanocapsules were prepared and demonstrated in their characterization particle size (206 ± 0.69 nm). The cytogenotoxicity evaluation was performed using the MTT, dichlorofluorescein, nitric oxide and dsDNA PicoGreen® assays. Antitumor efficacy assays in MCF-7 cells demonstrated that free oil and tucumã nanocapsules had IC50 of 130 and 50 µg/mL, respectively. Thus, previous studies of toxicity are relevant, as they generate future subsidies, aiming at the potential application of nanostructures and in addition, the promising effect of NCs of tucumã oil on the antiproliferative effect in breast adenocarcinoma cells was evidenced.

Açaí (Euterpe oleracea Mart.) as a Potential Anti-neuroinflammatory Agent: NLRP3 Priming and Activating Signal Pathway Modulation.

Neurological disorders have been demonstrated to be associated with mitochondrial dysfunction. This impairment may lead to oxidative stress and neuroinflammation, specifically promoted by NLRP3 expression. Açaí (Euterpe oleracea Mart.) has been studied in this field, since it presents important biological activities. We investigated açaí extract's anti-neuroinflammatory capacity, through NLRP3 inflammasome modulation. Microglia (EOC 13.31) were exposed to LPS and nigericin, as agents of inflammatory induction, and treated with açaí extract. Additionally, we used lithium (Li) as an anti-inflammatory control. Three different experiment models were conducted: (1) isolated NLRP3 priming and activation signals; (2) combined NLRP3 priming and activation signals followed by açaí extract as a therapeutic agent; and (3) combined NLRP3 priming and activation signals with açaí extract as a preventive agent. Cells exposed to 0.1 µg/mL of LPS presented high proliferation and increased levels of NO, and ROS, while 0.1 µg/mL of açaí extract was capable to reduce cellular proliferation and recover levels of NO and ROS. Primed and activated cells presented increased levels of NLRP3, caspase-1, and IL-1ß, while açaí, Li, and orientin treatments reversed this impairment. We found that açaí, Li, and orientin were effective prophylactic treatments. Preventative treatment with Li and orientin was unable to avoid overexpression of IL-1ß compared to the positive control. However, orientin downregulated NLRP3 and caspase-1. Lastly, primed and activated cells impaired ATP production, which was prevented by pre-treatment with açaí, Li, and orientin. In conclusion, we suggest that açaí could be a potential agent to treat or prevent neuropsychiatric diseases related to neuroinflammation.

Achyrocline flaccida essential oil from Brazil: phytochemical composition, genotoxicity, protective effects on Caenorhabditis elegans, and antimycobacterial activity.

Achyrocline flaccida (Weinm) DC. essential oil was obtained by hydrodistillation of wild flowers from southern Brazil. We explored, for the first time, the phytochemical composition, toxicity, resistance to oxidative stress in Caenorhabditis elegans, and antimycobacterial activities of A. flaccida essential oil. Twenty-four compounds were identified by GC-FID-MS and the major constituents identified were α-pinene (41.10%) and caryophyllene (30.52%). The essential oil showed no signs of genotoxicity in the comet assay and presented relevant antioxidant capacity since it prevented ROS production in the C. elegans model. Furthermore, the minimal inhibitory concentrations (MIC) results showed that M. abscessus, M. massiliense, and M. fortuitum had their growth inhibited by A. flaccida essential oil. Therefore, the essential oil of this plant is a promising alternative in the search for new compounds capable of decreasing oxidative stress and treating mycobacteriosis.

Hydroalcoholic extract of leaf of Arachis hypogaea L. (Fabaceae) did not induce toxic effects in the repeated-dose toxicity study in rats.

Arachis hypogaea L. (peanut) leaf is traditionally used for the treatment of insomnia in Asia. However, studies describing the safety and toxicity profile for this plant preparation are limited. Thus, the goal of this study was to investigate the toxicity of peanut leaf hydroalcoholic extract (PLHE) repeated treatment. The extract was administered orally (100, 300 or 1000 mg/kg) in male and female Wistar rats for 28 days (OECD guideline 407). PLHE treatment did not cause mortality or weight variation in the animals. Also, there was no alteration on locomotor activity (open field test), motor coordination (rotarod test), or anxiety behaviour (elevated plus-maze test). Male rats had a reduction in relative liver weight (100 mg/kg) and an increase in total kidney weight (1000 mg/kg), but there was no change in biochemical and haematological parameters after PLHE treatment. Free extracellular double-stranded DNA (dsDNA) levels was also evaluated, but PLHE treatment did not increase this parameter in rat organs. Also, the dose of 1000 mg/kg of PLHE significantly increased the total thiols in the liver of females compared with the control animals. Thus, PLHE did not induce toxicity after repeated exposure for 28 days in rats.

Phytochemical study, an evaluation of the antioxidant potential and the antimicrobial activity of Inga semialata (Vell.) C. Mart. hydroalcohol extract.

Inga semialata (Vell.) C. Mart. belongs to the family Fabaceae. It is known for its therapeutic properties, highlighting its antimicrobial and antioxidant potential. The objective of the present work was to obtain crude extract leaves of Inga semialata, to identify and quantify active compounds, to evaluate the antioxidant potential of the crude extract in vitro, as well as to determine its antimicrobial activity. The crude extract was obtained by the maceration process. The identified and quantified of compounds present in the crude extract of Inga semialata was performed by high performance liquid chromatography. The evaluation of the antioxidant potential of the extract was realized by in vitro tests (DPPH, diacetate dichlorofluorescein test and nitric oxide test) and the evaluation of the antimicrobial activity was carried out using the minimum inhibitory concentration methodology.

Peanut leaf extract has antioxidant and anti-inflammatory activity but no acute toxic effects.

Arachis hypogaea L. (peanut) leaves have been popularly used for the treatment of insomnia and inflammation, but no toxicological study has been performed for this plant preparation. This study aimed to examine the phytochemical composition of peanut leaf hydroalcoholic extract (PLHE) and describe its potential toxic effects and antioxidant and anti-inflammatory properties. The qualitative chemical analysis of PLHE by UHPLC-ESI-HRMS allowed the identification of eight metabolites types (totaling 29 compounds). The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay revealed that PLHE had strong antioxidant effects; it also exhibited nitric oxide (NO)-scavenging capacity. Human peripheral blood mononuclear cells (PBMCs) exposed to PLHE showed no reduced cell viability or increased free double-stranded DNA, NO, or reactive species production. PLHE reversed the cytotoxicity, pro-inflammatory (release of interleukin-1ß), and pro-oxidant effects of H2O2 on human PBMCs. Acute PLHE toxicity analysis was performed in vivo using the Organization for Economic Co-operation and Development (OECD) 423 guidelines. PLHE single injection (2000 mg/kg, intragastric) did not cause mortality or morbidity or induce changes in hematological or biochemical parameters after 14 days of administration. Thus, PLHE could be a source of bioactive compounds and possesses antioxidant and anti-inflammatory properties without elicitin cytotoxicity or genotoxicity in human PBMCs or acute toxicity in rats.

Glycerol monolaurate nanocapsules for biomedical applications: in vitro toxicological studies.

The glycerol monolaurate (GML) is a surfactant used in the food industry and has potent antimicrobial activity against many microorganisms; however, the use of GML is not expanded due its high melting point and poor solubility in water. The aim of the study was to produce, characterize, and evaluate in vitro the cytotoxicity of GML and GML nanocapsules. The GML nanocapsules were produced and characterized by a mean diameter, zeta potential, and polydispersity index. The cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, thiobarbituric acid reactive substances (TBARS), and hemolytic activity. The genotoxicity was verified by comet assay. The physicochemical parameters showed a mean diameter of 192.5 ± 2.8 nm, a polydispersity index of 0.061 ± 0.018, and a zeta potential about - 21.9 ± 1 mV. The viability test demonstrated the protector effect of GML nanocapsule compared with the GML on peripheral blood mononuclear cells (PBMC) and VERO cells (isolated from kidney epithelial cells extracted from an African green monkey). A reduction in lipid peroxidation and lactate dehydrogenase release in GML nanocapsule-exposed cells compared with GML treated cells was observed. The damage on erythrocytes was addressed in treatment with GML, while the treatment with GML nanocapsules did not cause an effect. Moreover, the comet assay showed that the GML-caused genotoxicity and GML nanocapsules do not demonstrate damage. The study showed the reduction of toxicity of GML nanocapsules by many methods used in antimicrobial therapy.