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A nanoemulsion-based nanogel of Citrus limon essential oil with leishmanicidal activity against Leishmania tropica and Leishmania major
Abstract
Cutaneous leishmaniasis is one of the diseases that severely affects human skin. Nanogels are the well-known formulation for topical drug delivery due to easy usage, high loading capacity, and physical and chemical stabilities. In this study, the toxicity effect of three essential oils, including Mentha piperita, Anethum graveolens, and Citrus limon (CLEO), was evaluated against Leishmania major and Leishmania tropica. Ingredients of CLEO as the most potent essential oil were identified using GC-MS analysis. The five major components were limonene (61.83%), sabinene (16.99%), trans-limonene oxide (3.08%), cis-limonene oxide (2.27%), and 1,2-cyclohexane diol, 1-methyl-4-(1-methylethenyl) (1.50%). The nanogel of CLEO (CLNgel) was prepared by the addition of car-bomer 940 (1% w/v) to the prepared nanoemulsion with a droplet size of 146 ± 12 nm. The viscosity of CLNgel was fitted with a regression of non-Newtonian materials, Car-reau-Yasuda. Interestingly, CLNgel at a concentration of 80 lg/mL reduced the viability of both species to 0%. Therefore, the prepared prototype can/could/would be used as an excellent nanoformulation for in vivo studies.
... However, the applied use of EOs is questioned due to volatility and lower efficiency compared to synthetic drugs. Formulating EOs into different nanoformulations has recently introduced as a promising strategy to combat the mentioned challenges [11,12]. ...
... TEM and DLS analyses of CZNE with the droplet size of 28 ± 4 nm and SPAN of 0.97 were depicted in Fig. 2; the droplet was spherical. In another study of our group, the nanoemulsion containing 20 μL of Citrus limon EO and 80 μL of tween 20 was prepared [12]. Its droplet size and SPAN were 146 nm and 0.96; the EO and surfactant ratio (1:4) in the mentioned report and this research are the same [12]. ...
... In another study of our group, the nanoemulsion containing 20 μL of Citrus limon EO and 80 μL of tween 20 was prepared [12]. Its droplet size and SPAN were 146 nm and 0.96; the EO and surfactant ratio (1:4) in the mentioned report and this research are the same [12]. ...
Major causatives for cutaneous leishmaniasis, the most common form of leishmaniasis, in the old world are Leishmania major and Leishmania tropica. Investigating the leishmanicidal effects of essential oils and preparing their nano/formulation is a promising approach for developing new green drugs. In this study, the ingredients of Cinnamomum zeylanicum essential oil were investigated using GC/MS analysis, and its antioxidant effect was then evaluated using the DPPH assay. Moreover, the leishmanicidal effect of the essential oil against L. major and L. tropica was investigated; obtained half-maximal inhibitory concentrations (IC50)s were 16.53 and 7.56 μg/mL. After that, a practical dosage form of C. zeylanicum, i.e., the nanoemulsion with a 52 ± 4 nm droplet size and a low droplet size distribution index (SPAN=0.97), was prepared. Interestingly, after treatment of both species with nanoemulsion, their viability was reduced to 0%. The prepared nanoformulation could be considered a potent anti-leishmanial agent for other species and in vivo studies.
... The impact of Vit-C and its derivatives like ascorbyl palmitate and acyl ascorbate on edible oils' oxidative stability was investigated in several studies (Galanakis et al., 2018;Kim et al., 2015;Martínez et al., 2013;Mohanan et al., 2018;Shadyro et al., 2017;Watanabe, 2015;Watanabe et al., 2005). There is no study to assess the effect of a microemulsion of Vit-C on virgin olive oil's oxidative stability to the best of our knowledge. ...
... Mohanan et al., 2018) For example, the significant (p < .05) higher induction time of samples containing 500 µg/ml Vit-C than that in samples containing 100 and 200 µg/ml TBHQ indicates its ability to increase the oxidative stability of virgin olive oil, which complies withMohanan et al., (2018) andWatanabe et al., (2005) studies. ...
This study aims to improve the oxidative stability of olive oil using microformulated vitamin‐C (Vit‐C). The microemulsion containing 10,000 µg/ml Vit‐C with a droplet size of 1,000 ± 68 nm was first prepared. Free radical scavenging of olive oil and olive oil containing blank microemulsion, different amounts of formulated Vit‐C (100–500 µg/ml), and TBHQ (100 and 200 µg/ml as a standard antioxidant) was around 90% during 21 days of incubation at 60°C. The oxidative stability of the mentioned samples during incubation was investigated using the rancimat test, and their quality criteria analysis was studied by peroxide and the acid values. Results showed that the sample's acid value containing 500 µg/ml of Vit‐C did not show significant differences (p < .05) with samples containing TBHQ. However, samples containing TBHQ's peroxide value were significant (p < .05) lower than samples containing 500 µg/ml of Vit‐C. Furthermore, the induction time of samples containing 500 µg/ml of Vit‐C was significantly (p < .05) higher than other treatments during incubation. Thus, the prepared microemulsion could be used as a natural antioxidant in the oil industry instead of harmful synthetic TBHQ.
... The main advantages of MEs/NEs in drug delivery systems include ease of preparation, optical clarity [4], increased drug bioavailability, decreased toxicity profile as well as taste masking capability. They are also able to solubilize lipophilic molecules in aqueous media [23,24]. ...
Microemulsions (MEs) and nanoemulsions (NEs) are dispersions of two immiscible liquids which are usually transparent/translucent. Several reports are available on uses of MEs/NEs to increase efficacy of the loaded active ingredient(s) in topical dosage forms. This review aims to describe brief applications of MEs/ NEs in common skin diseases as well as skincare products. Advantages of MEs/NEs in comparison with the traditional bulk form, including their improved efficacy and safety, have been discussed to highlight the importance of use of such delivery systems. The review briefs mechanism of action of MEs/NEs in enhancing delivery of the cargo. Furthermore, applications of MEs/NEs in common skin diseases including infectious rashes, pigmentation disorders (hyperpigmentaion and hypopigmentation), wound healing, skin cancers and scaling patches and plaques/papulosquamous disorders (psoriasis, atopic dermatitis and acne) have been discussed. MEs/NEs in skin care products have also been reviewed here.
... However, they still need to be improved for better skin penetration. 151 On the other study the nanogel at a concentration of 80 µg/mL reduced the viability of the tested parasitic infections to 0%. 152 This is very promising. Nanogels are evaluated also on the treatment of non-healing chronic wounds such as chronic diabetic ulcers. ...
A nanogel is a cross-linked nano-sized, a three-dimensional network of hydrophilic polymers with an ability to swell by holding large amount of water while maintaining the structure due to chemical or physical cross-linking of individual polymer chains. Nanogels can be made up of synthetic and/or natural polymers resulting in a cationic, anionic, or neutral system depending on the bound groups’ charges. Currently, these materials are receiving tremendous attention in research due to their properties. They are extensively investigated as carriers in the biomedical field. At present, there is an expansion of research into dermatologic treatment due to a critical need for new treatment options to treat skin diseases. The skin itself provides a natural barrier against particle penetration for topical delivery. However, it also offers a potential approach for the delivery of therapeutics, especially in diseased skin via the openings of hair follicles. Recent innovation might be achieved in the field of dermatological treatment with improvement in the dermal localization of bio-actives into the affected skin region. This report looks at what has been done in the investigation of nanogels as drug carriers for topical therapy.
... Subsequently, Zarenezhad et al. analyzed that the Citrus Limon Nanogel (CLN gel) is the most potent essential oil among Anethum graveolens and Mentha piperita against Leishmania major and Leishmania tropica. This evaluation proved the efficacy of CLN gel against both species [92]. Likewise, Ghanbariasad et al. formulated NE using Citrus sinensis essential oil and concluded its IC 50 values against promastigotes of Leishmania tropica and L. major, which were 151.13 and 108.31 ug/ml, respectively. ...
The global shift in lifestyle has prompted health agencies to redirect their focus from poverty-related diseases to the emergence of lifestyle diseases prevalent in privileged regions. As a result, these diseases have been labeled as "neglected diseases," receiving limited research attention, funding, and resources. Neglected Tropical Diseases (NTDs) encompass a diverse group of vector-borne protozoal diseases that are prevalent in tropical areas worldwide. Among these NTDs is leishmaniasis, a disease that affects populations globally and manifests as skin abnormalities, internal organ involvement, and mucous-related abnormalities. Due to the lack of effective and safe medicines and vaccines, it is crucial to explore alternative resources. Phytomedicine, which comprises therapeutic herbal constituents with anti-leishmanial properties, holds promise but is limited by its poor physicochemical properties. The emerging field of nanomedicine has shown remarkable potential in revitalizing the anti-leishmanial efficacy of these phytoconstituents. In this investigation, we aim to highlight and discuss key plant constituents in combination with nanotechnology that have been explored in the fight against leishmaniasis.
... There are also other species of the genus Mentha with antileishmanial properties on promastigotes of various species of Leishmania. EOs from M. australis and M. microphylla have antileishmanial effects on L. major [40], M. pulegium on L. major, L. infantum and L. tropica [41], M. x piperita on L. infantum and L. donovani [42,43], and M. cervina on L. infantum [42,44]. However, none of the mentioned EOs had piperitenone oxide as a major component. ...
Kinetoplastida is a group of flagellated protozoa characterized by the presence of a kinetoplast, a structure which is part of a large mitochondria and contains DNA. Parasites of this group include genera such as Leishmania, that cause disease in humans and animals, and Phytomonas, that are capable of infecting plants. Due to the lack of treatments, the low efficacy, or the high toxicity of the employed therapeutic agents there is a need to seek potential alternative treatments. In the present work, the antiparasitic activity on Leishmania infantum and Phytomonas davidi of 23 essential oils (EOs) from plants of the Lamiaceae and Asteraceae families, extracted by hydrodistillation (HD) at laboratory scale and steam distillation (SD) in a pilot plant, were evaluated. The chemical compositions of the EOs were determined by gas chromatography-mass spectrometry. Additionally, the cytotoxic activity on mammalian cells of the major components from the most active EOs was evaluated, and their anti-Phytomonas and anti-Leishmania effects analyzed. L. infantum was more sensitive to the EOs than P. davidi. The EOs with the best anti-kinetoplastid activity were S. montana, T. vulgaris, M. suaveolens, and L. luisieri. Steam distillation increased the linalyl acetate, β-caryophyllene, and trans-α-necrodyl acetate contents of the EOs, and decreased the amount of borneol and 1,8 cineol. The major active components of the EOs were tested, with thymol being the strongest anti-Phytomonas compound followed by carvacrol. Our study identified potential treatments against kinetoplastids.
... However, low viscosity is their only challenge for topical drug delivery. Nanoemulsionbased nanogels have thus been introduced as a promising dosage form in topical drug delivery; they exploit the advantages of nanoemulsion and improve their viscosity and stability [42,43]. Nowadays, nanogels have been widely used to improve the topical delivery of hydrophobic drugs. ...
Background
Topical drug delivery using nanoemulsions and nanogels is a promising approach to treating skin disorders such as melanoma.
Methods
In this study, the chemical composition of Mentha pulegium essential oil with five major compounds, including pulegone (68.11%), l-menthone (8.83%), limonene (2.90%), iso-pulegone (2.69%), and iso-menthone (1.48%) was first identified using GC-MS (Gas chromatography–Mass Spectrometry) analysis. Afterward, a nano-scaled emulsion containing the essential oil with a droplet size of 7.70 ± 1 nm was prepared. Nanogel containing the essential oil was then prepared by adding (2% w/v) carboxymethyl cellulose to the nano-scaled emulsion. Moreover, the successful loading of M. pulegium essential oil in the nano-scaled emulsion and nanogel was confirmed using ATR-FTIR (Attenuated total reflectance-Fourier Transform InfraRed) analysis. Then, human A375 melanoma cells were treated with different concentrations of samples, the MTT assay evaluated cell viability, and cell apoptosis was confirmed by flow cytometry. In addition, the expression of apoptotic and anti-apoptotic genes, including Bax and Bcl-2, was evaluated using the qPCR (quantitative Polymerase Chain Reaction) technique.
Results
The results showed that cell viability was reduced by 90 and 45% after treatment with 300 μg/mL of the nanogel and nano-scaled emulsion. As confirmed by flow cytometry, this effect was mediated by apoptosis. Furthermore, gene expression analysis showed up-regulation of Bax and down-regulation of Bcl-2 genes. Therefore, the prepared nanogel, with high efficacy, could be considered a potent anticancer agent for supplementary medicine and in vivo research.
... In short, a 6890 networked is used as the carrier gas. The EOs components were identified using the method described in our previous report [27]. ...
Since synthetic chemotherapeutic drugs produce a certain degree of drug resistance and due to their common side effects, such as damage to hematopoietic cells and hair loss, it is necessary to use herbal medicine as a substrate to develop new anticancer drugs. The ingredients of three essential oils (EO) were identified using gas chromatography–mass spectrometry (GC-MS) analysis. Their anticancer activities have been investigated on four human breast cancer cell lines, including MCF-7, MDA-MB-175, MDA-MB-231, and MDA-MB-468. In addition, their antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The three plants were investigated for identifications of the ingredients of their EOs, and major ingredients were identified in each plant as alpha-phellandrene (26.75 %) in Anethum graveolens L., limonene (61.83 %) in Citrus limon (L.) Osbeck, and zingiberene (30.28 %) in Zingiber officinale Roscoe. Among the EOs, C. limon was significantly more effective than others; its half-maximal inhibitory concentration (IC50) on MCF-7 was obtained at 201 µg.mL-1. Furthermore, Z. officinale EO showed a higher antioxidant activities in comparison to the two other EOs. Considering the antioxidant and anticancer effects of the EOs, they could be further investigated as a possible complementary medicine in cancer.
... Essential oils are volatile fat-soluble compounds derived from secondary plant metabolism (Carvalho et al., 2017;Lai et al., 2007;Manconi et al., 2016;Silva et al., 2018). Over the last decade, the antiparasitic potential of EOs has been investigated and is shown to be promising, both in dispersion or incorporated into nanocarriers to improve their properties (Pereira et al., 2021;Sampaio et al., 2019;Zarenezhad et al., 2021). Essential oils are composed mainly of terpenes and their derivatives, and can be found in specialized secretory structures such as glands, oil channels, and differentiated parenchymal cells (Omonijo et al., 2018;Sharifi-Rad et al., 2017). ...
Chagas Disease and Leishmaniasis are neglected parasitic diseases that constitute a major public health problem. In the search for new therapeutic alternatives for such pathologies, the essential oil of the leaves of Psidium brownianum Mart ex DC was investigated regarding its chemical composition, antiparasitic, and cytotoxic effects. The chemical composition of the oil was analyzed by gas chromatography coupled to mass spectrometry (GC/MS), showing two major constituents: Isogermafurene (52.93%) and Germacrone (16.02%). In antiparasitic activity, the oil was tested against the epimastigote forms of Trypanosoma cruzi, revealing 57.05% inhibition at the highest tested concentration (1000 μg/mL). In regard to antiparasitic activity against promastigote forms of Leishmania braziliensis and Leishmania infantum, it obtained 92.61% and 84.16% inhibition, respectively, at the highest concentrations (1000 μg/mL). As for the cytotoxic effects, it showed high cytotoxicity, with IC50 = 328.9 μg/mL. The inhibitory concentration (IC50) obtained the best result for the promastigote forms of L. braziliensis (IC50 = 37.53 μg/mL), as well as the selectivity index (SI = 8.76). Such results generate perspectives for new research and may contribute to more effective drug discoveries.
... DLS and TEM analyses of LNCsNPs with a particle size of 160 ± 9 and SPAN value of 0.96 are illustrated in Fig. 1. Besides, the mentioned analyses for TACsNPs with a particle size of 158 ± 7 nm SPAN 0.96 are depicted in Fig. 2. It is noteworthy that a SPAN value less than 1 is considered a narrow particle size distribution (Zarenezhad et al. 2020); both nanoformulation thus had a narrow particle size distribution. ...
Malaria is still a dreadful vector-borne disease; the excessive use of chemical insecticides has led to resistance in vector mosquitoes, especially Anopheles stephensi. On the other hand, the lower effectiveness of essential oils (as green alternatives) compared to synthetic ones and the volatility of their ingredients is limited their use in adoption for eradication of these vectors. In this study, the chemical composition and larvicidal effects of essential oils of Laurus nobilis and Trachyspermum ammi against A. stephensi were investigated. An attempt was then made to improve their efficacy by preparing chitosan nanoparticles containing each essential oil. Chitosan nanoparticles containing T. ammi essential oil with a particle size of 158 ± 7 nm and narrow particle size distribution (SPAN < 1) showed more larvicidal effects than samples with a lethal concentration of 50 (LC50) 13.67 µg/mL. This formulation could be introduced as a potent and green candidate against other mosquitoes and potential field application scope.
The occurrence of infectious parasitic disease is the leading driver of mortality worldwide. Treatment of such parasitic disease is challenging due to the minimal target bioavailability of antiparasitic drugs, poor cellular uptake, nonspecific distribution at the target site and rapid elimination from the body. Further antiparasitic drug toxicity and prolonged therapeutic regimens also concerns us. Leading trends in nanotechnology can overpower these shortcomings in the form of an ideal nanocarrier system that can be designed and fabricated accordingly, where new formulations and the existing antiparasitic drugs in nano-sized delivery vehicle can be more promising in terms of minimized non-specific drug accumulation, desired antiparasitic drug availability at the site of action, reduced therapeutic dose and duration that is to be delivered etc. Through this chapter, we have highlighted the major challenges of conventional treatment approaches and presented nanotechnology as an imminent alternative treatment approach for the infectious parasitic disease. However, the unification of these two-research areas as “nano-antiparasitic medicines” can progress as a therapeutic strategic plan, minimising the burden of individuals suffering from this worldwide.
Negligence in treating veterinary parasitic infection (VPI) has caused 50% of livestock loss as per the World Organization for Animal Health (WOAH). Only five major companies, including Zoetis, MSD AH, Elanco, Boehringer Ingelheim AH, and Bayer AH, are involved in animal anti-parasitic drug development. New drug discovery and development involve uncertainty and tremendous cost. Existing drugs against VPI are associated with drawbacks, including drug resistance, toxicity, non-specific delivery, non-adherence, non-compliance, unfavorable physicochemical properties, low bioavailability, and half-life. Nanotechnological intervention with an appropriate choice of excipients modulates the drug’s physicochemical properties. Moreover, it surpasses existing drawbacks, overcomes host (primary) and parasitic (secondary) cell barriers, stimulates primary defense mechanisms, and elicits long- acting and targeted delivery with reduced toxicity and enhanced efficacy. Furthermore, the nanoparticles overcome the P-glycoprotein receptors and drug resistance. This chapter elaborates on various nano-platform technologies, including liposomes, polymer- and lipid-based nanoparticles, nanoemulsions, nanosuspensions, and surface-conjugated nanoparticles loaded with natural/synthetic anti-parasitic drugs for treatment against VPI. Additionally, the nanovaccine targeting prominent Toll-like receptors (TLR) through TLR ligand and nanobodies has been succinctly elaborated. To conclude, careful consideration and future exploration are indispensable for nanomedicines against the treatment and prevention of VPI.
Medicinal chemists around the world have been inspired by nature and have successfully extracted chemicals from plants. Research on enzymatic modifications of naturally occurring compounds has played a critical role in the search for biologically active molecules to treat diseases.
This book set explores compounds of interest to researchers and clinicians. It presents a comprehensive analysis about the medicinal chemistry (drug design, structure-activity relationships, permeability data, cytotoxicity, appropriate statistical procedures, molecular modelling studies) of different compounds. Each chapter brings contributions from known scientists explaining experimental results which can be translated into clinical practice.
Volume 2 gives (1) a detailed overview of the sesquiterpenes polypharmacology, (2) an interesting journey around the world of cannabinoids that reveals the development of new synthetic Δ9-THC derivatives, (3) the design of specific formulations to overcome the volatility of small sized terpenes-based essential oils, (4) an update on the latest generations of endoperoxides endowed with antimalarial activity and finally (5) a summary of MedChem strategies to fix the most common issues in formulating terpene derivatives (like low potency and poor solubility).
The objective of this book set is to fulfill gaps in currently acquired knowledge with information from the recent years. It serves as a guide for academic and professional researchers and clinicians.
The human anaerobic or microaerophilic protists Giardia duodenalis, Entamoeba histolytica, and Trichomonas vaginalis are classified as amitochondriate parasites, a group of unicellular organisms that lack canonical mitochondria organelles. These microorganisms suffered adaptations to survive in hostile microenvironments and together represent an increasing threat to public health in developing countries. Nevertheless, the current therapeutic drugs to manage the infections are scarce and often cause several side effects. Furthermore, refractory cases associated with the emergence of parasitic resistance are concerns that guide the search for new pharmacological targets and treatment alternatives. Herein, essential oils and terpenic compounds with activity against amitochondriate parasites with clinical relevance are summarized and insights into possible mechanisms of action are made. This review aims to contribute with future perspectives for research with these natural products as potential alternatives for the acquisition of new molecules for the treatment of amitochondriate protists.
Background
Cinnamon ( Cinnamomum zeylanicum ) and Clove ( Syzygium aromaticum ) essential oils are two medicinally important plant-derived substances with a wide range of biological properties. Besides, nanoemulsion-based gels have been widely used to increase topical drug delivery and effectiveness.
Methods
This study aimed to explore the anti-inflammatory effect (paw edema test) and the anti-nociceptive effect (hot plate and formalin test) of nanoemulsion-based gels containing the essential oils in the animal model. Cinnamon and Clove essential oils nanoemulsions with droplet sizes of 28 ± 6 nm and 12 ± 3 nm were first prepared. By adding carboxymethylcellulose (3.5% w/v), the nanoemulsions were then gelified. Finally, the nanogels were characterized by ATR-FTIR analysis and were used as topical pre-treatment before induction of inflammation or pain in acute and chronic analgesic experimental studies.
Results
The paw edema and formalin findings showed that the nanogels formulations possess significant anti-nociceptive and anti-inflammatory effects.
Conclusion
The prepared nanogels could be considered as analgesic drugs for inhibiting the inflammation and pain of diseases.
Background and objectives:
Plant-derived essential oils (EOs) shave many usages in health and medicine, such as antibacterial agents. The aim of this study was the improvement of antibacterial activities of two EOs using nanotechnology.
Materials and methods:
Antibacterial activity was investigated on four important human pathogenic bacteria using the 96-well plate microdilution method, a quantitative approach. Eleven formulations were prepared using each of the EOs. Eventually, the best nanoformulation with the smallest particle size and polydispersive indices (PDI and SPAN) was selected using each EO for further investigations. Moreover, two microemulsions with similar ingredients and the same portion in comparison with two selected nanoemulsions were also prepared. Antibacterial activity of each EO was compared with its micro- and nano-emulsions.
Results:
The antibacterial efficacy of Zataria multiflora EO (ZMEO) was significantly better than Mentha piperita EO (MPEO). Besides, the antibacterial activity of nanoemulsion of ZMEO with a particle size of 129 ± 12 nm was significantly better than no- and micro-formulated forms of ZMEO. Interestingly, the efficiency of MPEO nanoemulsion (160 ± 25 nm) was also significantly better than MPEO and its micro-formulated form.
Conclusion:
Regardless of the intrinsic antibacterial property of two examined EOs, by formulating to nanoemulsion, their efficiencies were improved. Nanoemulsion of ZMEO introduced as an inexpensive, potent and green antibacterial agent.
This review presents important botanical, chemical and pharmacological characteristics of Citrus limon (lemon)—a species with valuable pharmaceutical, cosmetic and culinary (healthy food) properties. A short description of the genus Citrus is followed by information on the chemical composition, metabolomic studies and biological activities of the main raw materials obtained from C. limon (fruit extract, juice, essential oil). The valuable biological activity of C. limon is determined by its high content of phenolic compounds, mainly flavonoids (e.g., diosmin, hesperidin, limocitrin) and phenolic acids (e.g., ferulic, synapic, p-hydroxybenzoic acids). The essential oil is rich in bioactive monoterpenoids such as D-limonene, β-pinene, γ-terpinene. Recently scientifically proven therapeutic activities of C. limon include anti-inflammatory, antimicrobial, anticancer and antiparasitic activities. The review pays particular attention, with references to published scientific research, to the use of C. limon in the food industry and cosmetology. It also addresses the safety of use and potential phototoxicity of the raw materials. Lastly, the review emphasizes the significance of biotechnological studies on C. limon.
Frequent use of synthetic larvicides has led to the development of resistance in many species of mosquitoes as well as risk of environmental pollution. Recently, encapsulating essential oils (EOs) in surfactants or polymers is being employed as an approach to control the volatility of EOs as green larvicides. In this research, components of tarragon (Artemisia dracunculus) essential oil were identified by GC-MS analysis. Forty-eight components were identified, with 5 major components including estragole (67.623%), cis-Ocimene (8.691%), beta-Ocimene Y (7.577%), Limonene (4.338%) and 3-Methoxy cinnam aldehyde (1.49%). Tarragon EO was encapsulated in chitosan nanocapsules using ionic gelation method and confirmed by FT-IR analysis. Encapsulation efficiency and size of the chitosan nanocapsules were determined 34.91 ± 2% and 203 ± 16 nm, respectively. For the first time, a long-lasting green larvicide was reported which remained active for 10 days, against Anopheles stephensi. Furthermore, cytotoxicity of the nanoformulation was found to be similar to that of temephos on human skin normal cells (HFFF2). This nanoformulation can be a good alternative for synthetic larvicides due to its long-lasting activity, proper effectiveness and also its green constituents.
The authors would like to make the following corrections to the published paper [...]
Objective:
To prepare a novel nanoemulsion- Carbopol® 934 gel for Eugenol, in order to prevent the periodontitis.
Material and methods:
Spontaneous emulsification method was used for the preparation of nanoemulsion in which it contain Eugenol (oil phase), Tween-80 (surfactant), and PEG (co-surfactant). To the development of best nanoemulsion, three-factor three-level central composite design was used in which %oil; %Smix and % water were optimized as independent variables. An optimized-nanoemulsion were converted to nanoemulsion-Carbopol® 934 gel.
Results:
5.5% oil, 35.5% Smix and 59.0% water were optimized as independent and dependent variables. Finally dependent variables optimized as a particle size (nm), PDI and %transmittance were observed 79.92 ± 6.33 nm, 0.229 ± 0.019, and 98.88 ± 1.31% respectively. The values of final results for dependent variables like particle size (nm), PDI and % transmittance were evaluated as 79.92 ± 6.33 nm, 0.229 ± 0.019, and 98.88 ± 1.31%, respectively. TEM and SEM showed a spherical shape of developed nanoemulsion with refractive index (1.63 ± 0.038), zeta potential (-19.16 ± 0.11), pH (7.4 ± 0.06), viscosity (34.28 ± 6 cp), and drug content of 98.8 ± 0.09%. After that a final optimized EUG-NE-Gel was assessed on the basis of their pH measurement, drug content, syringeability, and mucoadhesion on the goat buccal mucosa. Optimized EUG-NE-Gel (Tween-80 and Carbopol® 934 used) showed the results, to improve the periodontal drug delivery of EUG in future.
Conclusion:
EUG-NE-Gel showed a significant role in anti-inflammatory activity, analgesic, and anesthetic, antibacterial, and treatment of periodontal disease.
Psoriasis is a proliferative inflammatory skin disorder with relapsing episodes. Herein, the efficacy of babchi oil (BO) loaded nanostructure gel was evaluated for antipsoriatic activity and oxidative stress biomarkers assessment using mouse tail model. BO was entrapped into cyclodextrin-based nanocarriers (360.9 ± 19.55 nm), followed by incorporation into a Carbopol gel and characterized for viscosity, spreadability and texture analysis. The gels were topically applied on mouse-tails once daily for fourteen days. Evaluation of antipsoriatic activity as determined by histopahological observations of orthokeratotic epidermis revealed two times higher efficacy of BO nanogel than the native BO gel. Further, significantly enhanced superoxide dismutase (SOD) and reduced glutathione (GSH) levels and diminished malondialdehyde (MDA) and nitrite (NO) levels revealed that nanogels played a major role in management of ROS associated in psoriasis pathogenesis. Hence, this study provides strong evidence for use cyclodextrin-based nanogels as safe and better delivery carrier of BO for management of psoriasis.
The complex viscosity of poly (lactic acid) (PLA)/poly (ethylene oxide) (PEO) blends and PLA/PEO/carbon nanotubes (CNT) biosensor as a function of frequency is measured and analyzed by Carreau–Yasuda model. This model correlates the complex viscosity to zero complex viscosity, relaxation time, power-law index as well as the shear stress and the width of the transition region between Newtonian and power-law behavior. The impacts of these parameters on the complex viscosity are justified to confirm the Carreau–Yasuda model. The calculations of Carreau–Yasuda model successfully agree with the experimental data at different frequency ranges. The prepared samples show different levels for parameters explaining the shear thinning behavior. A high zero complex viscosity, poor relaxation time, high power-law index, low frequency and a wide transition region between Newtonian and power-law behavior enhance the complex viscosity of samples. Among the studied parameters, the power-law index and the width of the transition region significantly change the complex viscosity. The prepared samples can develop the nano-bio-sensors for detection of various diseases such as cancer.
Leishmaniasis is a neglected tropical disease caused by members of the Leishmania genus of parasitic protozoa that cause different clinical manifestations of the disease. Current treatment options for the cutaneous disease are limited due to severe side effects, poor efficacy, limited availability or accessibility, and developing resistance. Essential oils may provide low cost and readily available treatment options for leishmaniasis. In-vitro screening of a collection of 52 commercially available essential oils has been carried out against promastigotes of Leishmania amazonensis. In addition, cytotoxicity has been determined for the essential oils against mouse peritoneal macrophages in order to determine selectivity. Promising essential oils were further screened against intracellular L. amazonensis amastigotes. Three essential oils showed notable antileishmanial activities: frankincense (Boswellia spp.), coriander (Coriandrum sativum L.), and wintergreen (Gualtheria fragrantissima Wall.) with IC50 values against the amastigotes of 22.1 ± 4.2, 19.1 ± 0.7, and 22.2 ± 3.5 μg/mL and a selectivity of 2, 7, and 6, respectively. These essential oils could be explored as topical treatment options for cutaneous leishmaniasis.
Current research reports the development, optimization and evaluation of Quercetin (QCT) loaded nanoemulsion (NE)-based gel for the effective rheumatoid arthritis (RA) management. The formulation of QCT- NE was developed using spontaneous emulsification techniques using the Box- Behnken experimental design. The cytotoxicity study and effect on TNF-α production were evaluated respectively on HIG-82 and RAW 264.7 cells. The study showed that QCT- NE has no toxic effect on synoviocytes and a strong inhibitory effect on LPS-induced TNF-α production. QCT- NE gel has confirmed adequate rheological behavior with a good texture profile and improved drug permeation compared to free QCT gel. In addition, the gel was found to be non-irritating and showed the inhibition of paw edema in rats induced by CFA over 24 h contrary to free QCT gel. In conclusion, the formulation of QCT- NE gel is an efficient topical treatment strategy for rheumatoid arthritis.
Skin is an important organ of the body due to offering an accessible and convenient site for drug administration. One of the disadvantages of transdermal drug delivery is the low penetration rate of drugs through the skin. Over the past decades, nanoparticles have been used as drug delivery systems to increase therapeutic effects or reduce toxicity. Encapsulation of drugs in nanoparticulate vesicles simplifies the transports of drugs into and across the skin.
Niosome nanoparticles are among these drug delivery systems, which have numerous applications in drug delivery and targeting. Niosomes are frequently used for loading drugs serving different purposes (e.g., anticancer, antiviral, and antibacterial agents). In recent years, there has been much research on the use of niosomal systems for the delivery of fungal drugs. A review of the literature investigating the advantages of niosomes in antifungal drug delivery can elucidate the efficiency and superiority of this nanocarrier over other nanocarriers.
Background
The aim of present study was to evaluate antileishmanial effects of Lavandula angustifolia (L. angustifolia) and Rosmarinus officinalis (R. officinalis) medicinal plants essential oils and nano-emulsions on Leishmania major (L. major).
Methods
The present study was performed in Leishmaniasis Reference Lab at Mazandaran University of Medical Sciences, Iran during 2016–2017. The IC50 values were calculated in both the promastigote and amastigote stages in J774 macrophage in comparison with meglumine antimoniate (MA) as positive control. In addition, cytotoxicity effects of essential oils and nano-emulsions prepared from both plants against macrophages were evaluated.
Results
Both essential oil and nano-emulsion of Lavander and Rosemary showed anti-leishmania activity on promastigote with IC50=0.11 μl/mL, IC50=0.26 μl/mL, and IC50=0.08 μl/mL respectively. Moreover, during amastigote assay, Lavander and Rosemary essential oils and nano-emulsion were effective at least in concentration of 0.12 μl/mL and 0.06 μl/mL (P=0.0001) respectively, on mean infected macrophages (MIR) and amastigotes in macrophages (P=0.0001). Additionally, cytotoxicity assay against macrophage revealed no toxicity on the host cells at IC50 concentrations.
Conclusion
The nano-emulsions of both plants were more effective than essential oil in both MIR and amastigote. However, in comparison with MA, the Lavander essential oil is more effective in reducing MIR. Rosemary nano-emulsion reduced MIR significantly more than MA in concentration of 0.25 μl/mL (P<0.001). Further investigations are recommended to evaluate the effect of these medicinal plants in murine models.
The physicochemical properties of four N-halomethylated and one non-halomethylated ammonium salts, with proven in vitro antileishmanial activity, were determined according to pharmaceutical standard procedures. The effectiveness and toxicity of these compounds were assessed in hamsters infected with Leishmania (Viannia) braziliensis and compared to that showed by meglumine antimoniate. Animals were followed during 90 days after the completion of treatment. Therapeutic response was determined according to the reduction of size of skin lesions. Toxicity was determined by the effect of compounds on body weight changes and serum levels of renal and hepatic metabolites. The effectiveness of compound 4 was similar to that showed by intralesional administration of meglumine antimoniate and better than that of the other ammonium salts. Levels of creatinine, alanine amino transferase, and blood urea nitrogen in serum were not significantly different between treatment groups, including healthy or untreated hamsters. Results imply that compound 4 has potential as a pharmaceutical active ingredient in the development of new and better formulations for the treatment of cutaneous leishmaniasis.
Essential oils are one of the most notorious natural products used for medical purposes. Combined with their popular use in dermatology, their availability, and the development of antimicrobial resistance, commercial essential oils are often an option for therapy. At least 90 essential oils can be identified as being recommended for dermatological use, with at least 1500 combinations. This review explores the fundamental knowledge available on the antimicrobial properties against pathogens responsible for dermatological infections and compares the scientific evidence to what is recommended for use in common layman’s literature. Also included is a review of combinations with other essential oils and antimicrobials. The minimum inhibitory concentration dilution method is the preferred means of determining antimicrobial activity. While dermatological skin pathogens such as Staphylococcus aureus have been well studied, other pathogens such as Streptococcus pyogenes , Propionibacterium acnes , Haemophilus influenzae , and Brevibacterium species have been sorely neglected. Combination studies incorporating oil blends, as well as interactions with conventional antimicrobials, have shown that mostly synergy is reported. Very few viral studies of relevance to the skin have been made. Encouragement is made for further research into essential oil combinations with other essential oils, antimicrobials, and carrier oils.
Citrus fruits have potential health-promoting properties and their essential oils have long been used in several applications. Due to biological effects described to some citrus species in this study our objectives were to analyze and compare the phytochemical composition and evaluate the anti-inflammatory effect of essential oils (EO) obtained from four different Citrus species. Mice were treated with EO obtained from C. limon, C. latifolia, C. aurantifolia or C. limonia (10 to 100 mg/kg, p.o.) and their anti-inflammatory effects were evaluated in chemical induced inflammation (formalin-induced licking response) and carrageenan-induced inflammation in the subcutaneous air pouch model. A possible antinociceptive effect was evaluated in the hot plate model. Phytochemical analyses indicated the presence of geranial, limonene, γ-terpinene and others. EOs from C. limon, C. aurantifolia and C. limonia exhibited anti-inflammatory effects by reducing cell migration, cytokine production and protein extravasation induced by carrageenan. These effects were also obtained with similar amounts of pure limonene. It was also observed that C. aurantifolia induced myelotoxicity in mice. Anti-inflammatory effect of C. limon and C. limonia is probably due to their large quantities of limonene, while the myelotoxicity observed with C. aurantifolia is most likely due to the high concentration of citral. Our results indicate that these EOs from C. limon, C. aurantifolia and C. limonia have a significant anti-inflammatory effect; however, care should be taken with C. aurantifolia.
Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. There are significant differences in the sensitivity of these species both to the standard drugs, for example, pentavalent antimonials and miltefosine, and those on clinical trial, for example, paromomycin. Over 60% of patients with visceral leishmaniasis in Bihar State, India, do not respond to treatment with pentavalent antimonials. This is now considered to be due to acquired resistance. Although this class of drugs has been used for over 60 years for leishmaniasis treatment, it is only in the past 2 years that the mechanisms of action and resistance have been identified, related to drug metabolism, thiol metabolism, and drug efflux. With the introduction of new therapies, including miltefosine in 2002 and paromomycin in 2005-2006, it is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy.
Context:
Natural products and their compounds are some of the most interesting sources of new drugs. Reviews have reported various pharmacological properties such as antimicrobial effects of Zataria multiflora Boiss (Lamiaceae).
Objective:
The present study investigates the chemical composition of Z. multiflora essential oil and evaluates its cytotoxic effects and anti-leishmanial activities against Leishmania tropica in an in vitro model.
Materials and methods:
The components of Z. multiflora oil were identified by gas chromatography/mass spectroscopy (GC/MS) analysis. Anti-leishmanial effects of the essential oil (0-100 μL/mL) and methanol extract of Z. multiflora (0-100 μg/mL) on promastigote forms as well as their cytotoxic activities against J774 cells were evaluated using MTT assay for 72 h. The leishmanicidal activity against amastigote forms of L. tropica was evaluated at the concentrations of 0-50 μg/mL in a macrophage model for 48 h.
Results:
The chemical analyses demonstrated that the main components of essential oil were thymol (41.81%), carvacrol (28.85%), and p-cymene (8.36%). Regarding leishmanicidal activity, the IC50 values for the essential oil and methanol extract were 3.2 μL/mL and 9.8 μg/mL against promastigote forms and 8.3 μL/mL and 34.6 μg/mL against amastigote forms, respectively. Essential oil (CC50 89.3 μL/mL) indicated a higher cytotoxic effect than the methanol extract (CC50 591.6 μg/mL) of Z. multiflora.
Conclusion:
The present study revealed the chemical composition of Z. multiflora that might be a natural source of new anti-leishmanial agents in terms of use against cutaneous leishmaniasis.
Development of many conditions and disorders, such as atherosclerosis and stroke, are dependent upon hemodynamic forces. To accurately predict and prevent these conditions and disorders hemodynamic forces must be properly mapped. Here we compare a shear-rate dependent fluid (SDF) constitutive model, based on the works by Yasuda et al in 1981, against a Newtonian model of blood. We verify our stabilized finite element numerical method with the benchmark lid-driven cavity flow problem. Numerical simulations show that the Newtonian model gives similar velocity profiles in the 2-dimensional cavity given different height and width dimensions, given the same Reynolds number. Conversely, the SDF model gave dissimilar velocity profiles, differing from the Newtonian velocity profiles by up to 25% in velocity magnitudes. This difference can affect estimation in platelet distribution within blood vessels or magnetic nanoparticle delivery. Wall shear stress (WSS) is an important quantity involved in vascular remodeling through integrin and adhesion molecule mechanotransduction. The SDF model gave a 7.3-fold greater WSS than the Newtonian model at the top of the 3-dimensional cavity. The SDF model gave a 37.7-fold greater WSS than the Newtonian model at artery walls located immediately after bifurcations in the idealized femoral artery tree. The pressure drop across arteries reveals arterial sections highly resistive to flow which correlates with stenosis formation. Numerical simulations give the pressure drop across the idealized femoral artery tree with the SDF model which is approximately 2.3-fold higher than with the Newtonian model. In atherosclerotic lesion models, the SDF model gives over 1 Pa higher WSS than the Newtonian model, a difference correlated with over twice as many adherent monocytes to endothelial cells from the Newtonian model compared to the SDF model.
Plants used for traditional medicine contain a wide range of substances that can be used to treat various diseases such as infectious diseases. The present study was designed to evaluate the antileishmanial effects of the essential oil and methanolic extract of Myrtus communis against Leishmania tropica on an in vitro model. Antileishmanial effects of essential oil and methanolic extract of M. communis on promastigote forms and their cytotoxic activities against J774 cells were evaluated using MTT assay for 72 hr. In addition, their leishmanicidal activity against amastigote forms was determined in a macrophage model, for 72 hr. Findings showed that the main components of essential oil were α-pinene (24.7%), 1,8-cineole (19.6%), and linalool (12.6%). Findings demonstrated that M. communis, particularly its essential oil, significantly (P<0.05) inhibited the growth rate of promastigote and amastigote forms of L. tropica based on a dose-dependent response. The IC50 values for essential oil and methanolic extract was 8.4 and 28.9 μg/ml against promastigotes, respectively. These values were 11.6 and 40.8 μg/ml against amastigote forms, respectively. Glucantime as control drug also revealed IC50 values of 88.3 and 44.6 μg/ml for promastigotes and amastigotes of L. tropica, respectively. The in vitro assay demonstrated no significant cytotoxicity in J774 cells. However, essential oil indicated a more cytotoxic effect as compared with the methanolic extract of M. communis. The findings of the present study demonstrated that M. communis might be a natural source for production of a new leishmanicidal agent.
Cutaneous leishmaniasis has various phenotypic aspects consisting of polymorphic amastigotes with different genetic ranges. Samples were collected from suspected patients of Khuzestan province. Prepared smears were stained, scaled, and measured using ocular micrometer. The Cyt b, ITS-rDNA, and microsatellite genes of Leishmania were amplified and Leishmania species were identified by molecular analyses. Of 150 examined suspected patients, 102 were identified to Leishmania species (90 L. major, nine L. tropica, and three unidentified). The amastigotes of 90 L. major had regular and different irregular shapes within three clinical lesions with no and/or low genetic diversity. Three haplotypes of Cyt b of L. major were found but no variation was observed using ITS-rDNA gene. Interesting findings were that all nine L. tropica had regular amastigote shapes with more genetic variations, also a patient which had coinfection of L. major, L. tropica, and Crithidia. At least two L. major and L. tropica were identified in suspected patients of the regions. Different irregular amastigotes' shapes of L. major can be explained by various reservoir hosts and vectors. In contrast, more molecular variations in L. tropica could be justified by genetic characters. Unidentified Leishmania could be mixed pathogens or nonpathogens with mammals' Leishmania or Crithidia.
Nanogels are being explored as drug delivery agents for targeting cancer due to their easy tailoring properties and ability to efficiently encapsulate therapeutics of diverse nature through simple mechanisms. Nanogels are proficiently internalized by the target cells, avoid accumulating in nontarget tissues thereby lower the therapeutic dosage and minimize harmful side effects. However, there is an urgent need for relevant clinical data from nanogels so as to allow translation of the nanogel concept into a viable therapeutic application for treatment of cancer. This review highlights some of the recent progress in nanogels as carrier in the field of nanomedicine for the treatment of cancer. The present review critically analyses the use of extracellular pH targeting for nanogels, siRNA delivery, PEGylated nanogels, multi-responsive nanogels and intracellular delivery of nanogels for improved therapy of cancer.
This paper presents a stabilized mixed finite ele-ment method for shear-rate dependent fluids. The nonlinear viscosity field is a function of the shear-rate and varies uni-formly in space and in time. The stabilized form is developed via application of Variational Multiscale (VMS) framework to the underlying generalized Navier–Stokes equation. Lin-ear and quadratic tetrahedral and hexahedral elements are employed with equal-order interpolations for the velocity and pressure fields. A variety of benchmark problems are solved to assess the stability and accuracy properties of the result-ing method. The method is then applied to non-Newtonian shear-rate dependent flows in bifurcating artery geometry, and significant non-Newtonian fluid effects are observed. A comparative study of the proposed method shows that the additional computational costs due to the nonlinear shear-rate dependent viscosity are only ten percent more than the computational cost for a Newtonian model.
Cases of human oro-mucosal leishmaniasis (ML) are mainly reported in areas where do perpetuate Leishmania (Viannia) braziliensis and the damages being mainly located to cartilaginous nasal septum and frontal portions of the nasal fossa. In Iran, an area free of any L.(V) braziliensis, three Leishmania species are known to perpetuate through distinct i) blood-feeding sand flies and ii) rodents or iii) canidae. Thus while establishing the diagnosis of any human oro-mucosal lesions, three Leishmania species- L. infantum, L. major, L .tropica-must be considered as potential etiological agents of these damages.
With these objectives in mind, features-such as localization, extent, severity of oro-mucosal lesions, and duration of symptom at time of diagnosis were recorded from 11 patients with respect to the presence or absence of cutaneous lesions in other body parts. The biopsy samples were collected from the oro-mucosal and cutaneous lesions and were processed for further identification of the Leishmania species.
The lesions ranged from mucosal nodules without ulceration, nodule with erosion, and shallow to deep ulcerations. Leishmania major was isolated from six (55%) cases showing lesion or scars. The scars were restricted to upper and lower extremities. For the five other patients who did not display any signs of former or active CL, L. major, L. tropica and L. infantum were isolated from their lesions.
In conclusion L. major, L. infantum, and L.tropica, regardless of common tropism, can be seen in mucosal tissues. However, L. major was the predominant species detected from the lesions in the nasal, gingival, and hard and soft palates, L. tropica was isolated from the gingival and lower lip lesions. Leishmania infantum was isolated from two severe cases of deep mucosal damaging processes displayed by the epiglottis, crycoarytenoid muscle, and laryngeal mucosa. One important finding was the association of L. major with active or scarred skin lesions.
The leishmanicidal and cytotoxic activity of ten essential oils obtained from ten plant specimens were evaluated.
Essential oils were obtained by the steam distillation of plant leaves without any prior processing. Cytotoxicity was tested on J774 macrophages and leishmanicidal activity was assessed against four species of Leishmania associated with cutaneous leishmaniasis.
Seven essential oils exhibited activity against Leishmania parasites, five of which were toxic against J774 macrophages. Selectivity indices of >6 and 13 were calculated for the essential oils of Ocimum basilicum and Origanum vulgare, respectively.
The essential oil of Ocimum basilicum was active against promastigotes of Leishmania and innocuous to J774 macrophages at concentrations up to 1600 µg/mL and should be further investigated for leishmanicidal activity in others in vitro and in vivo experimental models.
Herbal medicines have been widely used all over the world since ancient times and have been recognized by physicians and patients for their better therapeutic value as they have fewer adverse effects as compared with modern medicines. Phytotherapeutics need a scientific approach to deliver the components in a sustained manner to increase patient compliance and avoid repeated administration. This can be achieved by designing novel drug delivery systems (NDDS) for herbal constituents. NDDSs not only reduce the repeated administration to overcome non-compliance, but also help to increase the therapeutic value by reducing toxicity and increasing the bioavailability. One such novel approach is nanotechnology. Nano-sized drug delivery systems of herbal drugs have a potential future for enhancing the activity and overcoming problems associated with plant medicines. Hence, integration of the nanocarriers as a NDDS in the traditional medicine system is essential to conflict more chronic diseases like asthma, diabetes, cancer, and others.
As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 countries and three territories (see 'Leishmaniasis Country Profiles Text S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21, S22, S23, S24, S25, S26, S27, S28, S29, S30, S31, S32, S33, S34, S35, S36, S37, S38, S39, S40, S41, S42, S43, S44, S45, S46, S47, S48, S49, S50, S51, S52, S53, S54, S55, S56, S57, S58, S59, S60, S61, S62, S63, S64, S65, S66, S67, S68, S69, S70, S71, S72, S73, S74, S75, S76, S77, S78, S79, S80, S81, S82, S83, S84, S85, S86, S87, S88, S89, S90, S91, S92, S93, S94, S95, S96, S97, S98, S99, S100, S101'). Additional information was collated during meetings conducted at WHO regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence. Mortality data were extremely sparse and generally represent hospital-based deaths only. Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year. Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis. These data should help to define control strategies and reinforce leishmaniasis advocacy.
Leishmaniasis is one of the most important parasitic infections, but current treatments are unsatisfactory due to their toxicity, cost and resistance. Therefore, the development of new antileishmanial compounds is imperative. Many people who live in endemic areas use plants as an alternative to treat the disease. In this paper, we characterised the essential oil from Piper auritum, evaluated its cytotoxicity and determined its antileishmanial activity. The chromatogram obtained by gas chromatography revealed 60 peaks and we found that safrole was the most abundant compound, composing 87% of the oil. The oil was active against the promastigotes of Leishmania major, Leishmania mexicana, Leishmania braziliensis and Leishmania donovani with a favourable selectivity index against peritoneal macrophages from BALB/c mice. The Piper-oil inhibited the growing of intracellular amastigotes of L. donovani with an IC50 value of 22.3 +/- 1.8 microg/mL. This study demonstrates the usefulness of the essential oils as a promising alternative to treat leishmaniasis.
Current therapy against leishmaniasis is unsatisfactory. Efficacious and safe new drugs are needed. In this study, we show the leishmanicidal effect of an essential oil from Chenopodium ambrosioides against Leishmania amazonensis.
The tested product had a potent inhibitory action against promastigote and amastigote forms, with 50% effective dose values of 3.7 and 4.6 microg/ml, respectively. The essential oil showed a moderate toxicity on macrophages from BALB/c mice. An optimal dose of 30 mg/kg/day was effective when administered during 15 days by intraperitoneal route to BALB/c mice infected experimentally.
These studies revealed a potential source for the discovery of novel drugs to combat the leishmaniasis based on the traditional medicine.
Leishmaniasis is a neglected parasitic protozoal disease that affects approximately 12 million people and represents a public health problem in Iran. The objectives of this study were to obtain the essential oil (EO) from Pulicaria vulgaris Gaertn. growing in Iran and to carry out in-vitro antileishmanial screening of the EO against promastigotes of Leishmania major and Leishmania infantum. The EO from the aerial parts of P. vulgaris was extracted by hydrodistillation. Serial dilutions of the EO were screened for in-vitro antileishmanial activity using 96-well microtiter plates. The P. vulgaris EO was active against the promastigote forms of L. major and L. infantum, with IC50 values of 244.70 and 233.65 μg/mL, respectively. Pulicaria vulgaris EO may serve as an alternative or complementary treatment for leishmaniasis.
The aim of present study was to design and optimize 0.1% adapalene loaded nano-emulsion to improve the efficacy of the drug efficacy and increase its user compliance. Effect of type and concentration of surfactants was studied on size of 0.1% adapalene loaded nano-emulsion. Optimized formulation was then evaluated for particle size, polydispersity index, morphology, viscosity, and pH. Subsequently, 1% carbopol® 934 was incorporated to the optimized formulation for preparation of its gel form. The efficacy and safety of 0.1% adapalene loaded nano-emulsion gel was assessed compared to marketed gel containing 0.1% adapalene. In-vitro studies showed that adapalene permeation through the skin was negligible in both adapalene loaded nano-emulsion gel and adapalene marketed gel. Furthermore, drug distribution studies in skin indicated higher retention of adapalene in the dermis in adapalene loaded nano-emulsion gel compared with adapalene marketed gel. Antibacterial activity against Propionibacterium acnes showed that adapalene loaded nano-emulsion is effective in reducing minimum inhibitory concentration of the formulation in comparison with tea tree oil nano-emulsion, and pure tea tree oil.
In vivo skin irritation studies showed absence of irritancy for adapalene loaded nano-emulsion gel. Also, blood and liver absorption of the drug, histological analysis of liver and liver enzyme activity of rats after 90 days' treatment were investigated. No drug was detected in blood/liver which in addition to an absence of any adverse effect on liver and enzymes showed the potential of adapalene loaded nano-emulsion gel as a novel carrier for topical delivery of adapalene.
Nanogels are innovative drug delivery system that can play an integral part in pointing out many issues related to old and modern courses of treatment such as nonspecific effects and poor stability. Nanogels may be defined as highly cross linked nano-sized hydrogels ranges from 20-200 nm. They can be administered through various routes, including oral, pulmonary, nasal, parenteral, intra-ocular etc. They have a high degree of drug loading capacity and it shows better permeation capabilities due to smaller size. They release the drug by pH responsive, thermosensitive, volume transition, photochemical internalization and Photoisomerization mechanism. They can be classified by stimuli responsive or non-responsive behavior and type of linkages present in the network chains of gel structure. Nanogel can be synthesized by Photolithographic, modified pullulan, emulsion polymerization, reverse microemulsion polymerization, inverse miniemulsion polymerization and free radical crosslinking polymerization technique. Nanogels can be used for the treatment of cancer, diabetes, inflammation and bone regeneration etc. Nanogels are the novel drug delivery systems for both hydrophilic and hydrophobic drugs.
Continuous use of chemical larvicides causes resistance in many species around the world and also environmental pollution. Nanoemulsions of herbal larvicides (such as essential oil based larvicides) are suitable alternatives for this purpose. However, no work so far has investigated the stability of a nanoemulsion after 100–200 times dilution and its effect on larvae of Anopheles stephensi, a major vector spreading malaria. Tarragon is a common medicinal plants and its essential oil had effective larvicidal activity. Different nanoemulsions of Tarragon essential oil were prepared using various amounts of surfactants and co-surfactants. For the first time, a comparison of larvicidal activity between two optimized preparations (particle sizes of 15.6 & 14.5 nm) with tarragon essential oil against Anopheles stephensi was performed. The components of Tarragon essential oil were identified by GC–MS analysis. Forty eight components were determined, with 5 major components including P-Ally anisole (67.623%), cis-Ocimene (8.691%), beta-Ocimene Y (7.577%), Limonene (4.338%) & 3-Methoxy cinnam aldehyde (1.49%). The bioassay of essential oil was performed, LC at 50 or 90% with values of 11.36 or 17.54 ppm, were calculated using probit analysis. No larvicidal effect was observed from nanoemulsion inactive ingredients (i.e. Tween 20 and isopropyl alcohol). Larvicidal activity of the most stable formulation after dilution (particle size 14.5 nm), showed significant increase compared to bulk of the oil and nanoemulsions with lesser stability profile after dilution. By designing and preparing a stable essential oil nanoformulation, against dilution, which takes the advantage of lesser volatile properties. And also, achieving to effective and environmentally friendly larvicides with low cost will be possible.
Copaiba oil is used as a popular medicine in the Amazonian forest region, especially due to its anti-inflammatory properties. In this paper, we describe the formulation of hydrogel containing copaiba oil nanoemulsions (with positive and negative charges), its skin permeation, and its anti-inflammatory activity in two in vivo models: mouse ear edema and rat paw edema. Three hydrogels were tested (Carbopol(®), hydroxyethylcellulose and chitosan), but only Carbopol(®) and hydroxyethylcellulose hydrogels presented good stability and did not interfere with the nanoemulsions droplet size and polydispersity index. In skin permeation assay, both formulations, positively charged nanoemulsion (PCN) and negatively charged nanoemulsion (NCN), presented a high retention in epidermis (9.76 ± 2.65 μg/g and 7.91 ± 2.46 μg/cm(2), respectively) followed by a smaller retention in the dermis (2.43 ± 0.91 and 1.95 ± 0.56 μg/cm(2), respectively). They also presented permeation to the receptor fluid (0.67 ± 0.22 and 1.80 ± 0.85 μg/cm(2), respectively). In addition, anti-inflammatory effect was observed to NCN and PCN with edema inhibitions of 69 and 67% in mouse ear edema and 32 and 72% in rat paw edema, respectively. Histological cuts showed the decrease of inflammatory factors, such as dermis and epidermis hyperplasia and inflammatory cells infiltration, confirming the anti-inflammatory effect from both copaiba oil nanoemulsions incorporated in hydrogel.
Inter-simple sequence repeats (ISSR), simple sequence repeats (SSR) and isozymes were used to measure genetic diversity and phylogenetic relationships among 95 Citrus L. accessions including 57 lemons [C. limon (L.) Burm. f.], related taxa, and three proposed ancestral species, C. maxima (Burm.) Merrill (pummelo), C. medica L. (citron), and C. reticulata Blanco (mandarin). The ancestry of lemons and several other suspected hybrids was also studied. Five isozyme and five SSR loci revealed relatively little variation among most lemons, but a high level of variation among the relatively distant Citrus taxa. Eight ISSR primers amplified a total of 103 polymorphic fragments among the 83 accessions. Similarity matrices were calculated and phylogenetic trees derived using unweighted pair-group method, arithmetic average cluster analysis. All lemons, rough lemons, and sweet lemons, as well as some other suspected hybrids, clustered with citrons. Most lemons (68%) had nearly identical marker phenotypes, suggesting they originated from a single clonal parent via a series of mutations. Citrons contributed the largest part of the lemon genome and a major part of the genomes of rough lemons, sweet lemons, and sweet limes. Bands that characterize C. reticulata and C. maxima were detected in lemons, suggesting that these taxa also contributed to the pedigree of lemon.
Context:
Eryngium foetidum L. (Apiaceae) is a traditional herb that has been used for numerous medicinal applications, including as a treatment for parasitic infections, especially in the Neotropics from where it originates.
Objective:
This study evaluates the in vitro leishmanicidal and cytotoxicity activities of isolated compounds based on a bioassay-guided fractionation approach.
Materials and methods:
Defatted aerial parts of E. foetidum were subjected to extraction with methanol followed by partitioning with n-hexane, ethyl acetate and 50% methanol. Then, the first two fractions were subsequently fractionated by column chromatography and HPLC. Compound identity was confirmed by mass spectrometry and NMR spectroscopy. Leishmania tarentolae (promastigotes) and L. donovani (amastigotes) were used as testing parasites. L6 rat myoblasts were used for cytotoxicity. All extracts and fractions were tested at 20 μg/mL.
Results:
The initial methanol extract showed 20% growth inhibition of L. tarentolae. Then, the n-hexane and ethyl acetate fractions were also active showing approximately 40% growth inhibition. From these two fractions, the following compounds were isolated: lasidiol p-methoxybenzoate (1), a daucane sesquiterpene; and 4-hydroxy-1,1,5-trimethyl-2-formyl-cyclohexadien-(2,5)-[α-acetoxymethyl-cis-crotonate] (2), a terpene aldehyde ester derivative. Compound 1 inhibited the growth of both L. tarentolae and L. donovani with IC₅₀ values of 14.33 and 7.84 μM, respectively; and showed no cytotoxicity (IC₅₀ > 50 μM). Compound 2 was inactive in the L. tarentolae assay (IC₅₀ > 50 μM).
Discussion and conclusion:
This study presented the bioassay-guided fractionation with the leishmanicidal and cytotoxicity activities of two compounds isolated for the first time from an Eryngium species.
The purpose of this study was to develop and characterize a successful colloidal soft nano-carrier viz. microemulsion system, for the transdermal delivery of an angiotensin II receptor blocker: olmesartan medoxomil. Different microemulsion formulations were prepared. The microemulsions were characterized visually, with the polarizing microscope, and by photon correlation spectroscopy. In addition, the pH and conductivity (σ) of the formulations were measured. The type and structure of microemulsions formed were determined using conductivity measurements analysis, Freezing Differential Scanning Calorimetry (FDSC) and Diffusion-Ordered Spectroscopy (DOSY). Alterations in the molecular conformations of porcine skin were determined using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) biophysical assessment. Olmesartan medoxomil delivery from the investigated formulations was assessed across porcine skin ex-vivo using Franz diffusion cells; the drug was analyzed by liquid chromatography mass spectroscopy (LC/MS/MS). A comparative pharmacokinetic study was done on healthy human subjects between the selected microemulsion and the commercial oral tablets. The physico-chemical and spectroscopic methods revealed the presence of water-in-oil and bicontinuous structures. Biophysical assessment demonstrated various stratum corneum (SC) changes. Olmesartan medoxomil was delivered successfully across the skin with flux achieving 3.65μgcm(-2)h(-1). Higher bioavailability compared to commercial oral tablets with a more sustainment behavior was achieved.
Leishmaniasis causes considerable mortality throughout the world, affecting more than 12 million people. Cymbopogon citratus (DC) Stapf, Family Poaceae, is a widely used herb in tropical countries and is also known as a source of ethnomedicines.
In this study, the inhibitory effect and the morphological and ultrastructural alterations on Leishmania amazonensis by the essential oil (EO) of C. citratus and its main constituent, citral, were evaluated. The results showed that the antiproliferative activity of EO on promastigotes
and axenic amastigotes, and intracellular amastigote forms of L. amazonensis was significantly better than citral, and indicated a dose-dependent effect. Neither compound showed a cytotoxic effect on
macrophage strain J774G8. The promastigote forms of L. amazonensis underwent remarkable morphological and ultrastructural alterations compared with untreated cultures. These alterations were
visible by light, scanning, and transmission electron microscopy of promastigotes treated with EO and citral at concentrations
corresponding to the IC50 (1.7 and 8.0 µg/ml) and IC90 (3.2 and 25 µg/ml), respectively, after 72h of incubation. This study revealed that citral-rich essential oil from C. citratus has promising antileishmanial properties, and is a good candidate for further research to develop a new anti-protozoan drug.
The aim of this pilot study was to investigate the anticaries activity of a nanoemulsion composed of soybean oil, water, Triton X-100 and cetylpyridinium chloride.
Tooth blocks (3 mm length x 3 mm width x 2 mm thickness) were cut from smooth surfaces of selected molar teeth using a water-cooled diamond wire saw. The blocks were randomly assigned to three experimental groups: (A) nanoemulsion, (B) 0.12% chlorhexidine gluconate, and (C) no treatment. The formation of dental caries in human tooth enamel was tested using a continuous flow dual-organism (Streptococcus mutans and Lactobacillus casei), biofilm model, which acts as an artificial mouth and simulates the biological and physiological activities observed within the oral environment. Experimental groups A and B were treated with their respective solutions once daily for 30 s on each occasion, while group C received no treatment. 10% sucrose was supplied every 6 h for 6 min to simulate meals and pH cycling. The experiment lasted for 5 days, and the tooth blocks were harvested and processed for demineralization assessment using transverse microradiography (TMR).
For both lesion depth and mineral loss, statistical analysis indicated that Emulsion was significantly lower than Control and Chlorhexidine, and Chlorhexidine was significantly lower than Control.
We conclude that cetylpyridinium-containing nanoemulsions appear to present a feasible means of preventing the occurrence of early caries.
In the present study, we selected in vitro populations of Leishmania Viannia guyanensis, L.V. braziliensis, L. Leishmania amazonensis and L.L. infantum chagasi that were resistant to potassium antimony tartrate (SbIII). The resistance index of these populations varied from 4- to 20-fold higher than that of their wild-type counterparts. To evaluate the stability of the resistance phenotype, these four resistant populations were passaged 37 to 47 times in a culture medium without SbIII. No change was observed in the resistance indexes of L.V. guyanensis (19-fold) and L.L. infantum chagasi (4-fold). In contrast, a decrease in the resistance index was observed for L.V. braziliensis (from 20- to 10-fold) and L.L. amazonensis (from 6- to 3-fold). None of the antimony-resistant populations exhibited cross-resistance to amphotericin B and miltefosine. However, the resistant populations of L.V. braziliensis, L.L. amazonensis and L.L. infantum chagasi were also resistant to paromomycin. A drastic reduction was observed in the infectivity in mice for the resistant L.V. guyanensis, L.L. amazonensis and L.V. braziliensis populations. The SbIII-resistant phenotype of L.V. braziliensis was stable after one passage in mice. Although the protocol of induction was the same, the SbIII-resistant populations showed different degrees of tolerance, stability, infectivity in mice and cross-resistance to antileishmanial drugs, depending on the Leishmania species.
The effect of different essential oils as well as of isolated mono- and sesquiterpenes on the viability of bloodstream forms of Trypanosoma brucei, promastigotes of Leishmania major and human HL-60 cells was evaluated using the Almar Blue assay. Of the 12 essential oils and 8 terpenes investigated, only three essential oils, Melissa officinalis (balmmint) oil, Thymus vulgaris (thyme) oil, and Melaleuca alternifolia (tea tree) oil were about 50-fold and 80-fold more toxic to bloodstream forms of T. brucei than to HL-60 cells, respectively. Terpinen-4-ol, the main compound of the Australian tea tree oil, was even 1000-fold more toxic to trypanosomes than to the human cells. On the other hand, none of the essential oils and terpenes tested were more toxic to promastigotes of L. major than to HL-60 cells.
Natural products are not only the basis for traditional or ethnic medicine. Only recently, they have provided highly successful new drugs such as Artemisinin. Furthermore, screening natural products found in all sorts of environments such as the deep sea, rain forests and hot springs, and produced by all sorts of organisms ranging from bacteria, fungi and plants to protozoa, sponges and invertebrates, is a highly competitive field where all of the major pharmaceutical companies are encountered. Already, many new natural product groups have revealed antiparasitic properties of surprising efficacy and selectivity, as will be shown in this review for plant-derived alkaloids, terpenes and phenolics. Many novel lead structures, however, have severe chemico-physical drawbacks such as poor solubility. Here, innovative drug formulations and carrier systems might help, as discussed by the authors in another article of this series.
The control of Leishmania infections relies primarily on chemotherapy. The arsenal of drugs available for treating Leishmania infections is limited and includes pentavalent antimonials, pentamidine, amphotericin B, miltefosine, fluconazole and few other drugs at various stages of their development process. In this review, we will discuss the latest results regarding resistance mechanisms to drugs used in the clinic against Leishmania infections.
We examined the anti-stress action of the essential oils of lavender, rose, and lemon using an elevated plus-maze task (EPM), a forced swimming task (FST), and an open field task (OFT) in mice. Lemon oil had the strongest anti-stress effect in all three behavioral tasks. We further investigated a regulatory mechanism of the lemon oil by pre-treatments with agonists or antagonists to benzodiazepine, 5-HT, DA, and adrenaline receptors by the EPM and the FST. The anti-stress effect of lemon oil was significantly blocked by pre-treatment with frumazenil, benzodiazepine receptor antagonist, or apomorphine, a nonselective DA receptor agonist. In contrast, agonists or antagonists to the 5-HT receptor and the alpha-2 adrenaline receptor did not affect the anti-stress effect of lemon oil. Buspirone, DOI, and mianserine blocked the antidepressant-like effect of lemon oil in the FST, but WAY100,635 did not. These findings suggest that the antidepressant-like effect of lemon oil is closely related with the 5-HTnergic pathway, especially via 5-HT(1A) receptor. Moreover, the lemon oil significantly accelerated the metabolic turnover of DA in the hippocampus and of 5-HT in the prefrontal cortex and striatum. These results suggest that lemon oil possesses anxiolytic, antidepressant-like effects via the suppression of DA activity related to enhanced 5-HTnergic neurons.
Leishmanicidal activity of a daucane sesquiterpene isolated from Eryngium foetidum
- P Rojas-Silva
Rojas-Silva P et al (2014) Leishmanicidal activity of a daucane
sesquiterpene isolated from Eryngium foetidum. Pharm Biol
52:398-401. https://doi.org/10.3109/13880209.2013.83707
Nanogels as novel drug delivery systems-a review
- H Yadav
- Al Halabi
- N Alsalloum
Yadav H, Al Halabi N, Alsalloum G (2017) Nanogels as novel drug
delivery systems-a review. J Pharm Pharm Res 1:52
Anti-inflammatory effect from a hydrogel containing nanoemulsified copaiba oil (Copaifera multijuga Hayne)
- L G Lucca
- LG Lucca