Alginate Nanoparticles Containing Cuminum cyminum and Zataria multiflora Essential Oils with Promising Anticancer and Antibacterial Effects.

Cancer and bacterial infections are major global health concerns driving the need for innovative medicines. This study investigated alginate nanoparticles loaded with essential oils (EOs) from Cuminum cyminum and Zataria multiflora as potential drug delivery systems. The nanoparticles were comprehensively characterized using techniques such as gas chromatography-mass spectrometry (GC-MS), dynamic light scattering (DLS), zetasizer, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and ultraviolet-visible spectroscopy (UV-Vis). Their biological properties against two human skin cancer cell lines (A-375 and A-431) and three bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) were also evaluated. Alginate nanoparticles containing C. cyminum and Z. multiflora EOs exhibited sizes of 160 ± 8 nm and 151 ± 10 nm, respectively. Their zeta potentials and encapsulation efficiencies were -18 ± 1 mV and 79 ± 4%, as well as -27 ± 2 mV and 86 ± 5%, respectively. The IC50 values against the tested cell lines and bacteria revealed superior efficacy for nanoparticles containing Z. multiflora EO. Considering the proper efficacy of the proposed nanoparticles, the straightforward preparation method and low cost suggest their potential for further in vivo studies.

The wound healing effect of polycaprolactone-chitosan scaffold coated with a gel containing Zataria multiflora Boiss. volatile oil nanoemulsions.

AIMS: Thymus plant is a very useful herbal medicine with various properties such as anti-inflammatory and antibacterial. Therefore, the properties of this plant have made this drug a suitable candidate for wound healing. In this study, hydroxypropyl methylcellulose (HPMC) gel containing Zataria multiflora volatile oil nanoemulsion (neZM) along with polycaprolactone/chitosan (PCL-CS) nanofibrous scaffold was used, and the effect of three experimental groups on the wound healing process was evaluated. The first group, HPMC gel containing neZM, the second group, PCL-CS nanofibers, and the third group, HPMC gel containing neZM and bandaged with PCL-CS nanofibers (PCL-CS/neZM). Wounds bandaged with common sterile gas were considered as control. METHODS: The nanoemulsion was synthesized by a spontaneous method and loaded into a hydroxypropyl methylcellulose (HPMC) gel. The DLS test investigated the size of these nanoemulsions. A PCL-CS nanofibrous scaffold was also synthesized by electrospinning method then SEM and contact angle tests investigated morphology and hydrophilicity/hydrophobicity of its surface. The animal study was performed on full-thickness skin wounds in rats, and the process of tissue regeneration in the experimental and control groups was evaluated by H&E and Masson's trichrome staining. RESULTS: The results showed that the nanoemulsion has a size of 225±9 nm and has an acceptable dispersion. The PCL-CS nanofibers synthesized by the electrospinning method also show non-beaded smooth fibers and due to the presence of chitosan with hydrophilic properties, have higher surface hydrophobicity than PCL fibers. The wound healing results show that the PCL-CS/neZM group significantly reduced the wound size compared to the other groups on the 7th, 14th, and 21st days. The histological results also show that the PCL-CS/neZM group could significantly reduce the parameters of edema, inflammation, and vascularity and increase the parameters of fibrosis, re-epithelialization, and collagen deposition compared to other groups on day 21. CONCLUSION: The results of this study show that the PCL-CS/neZM treatment can effectively improve wound healing.

Anticancer, antioxidant, and antibacterial effects of nanoemulsion of Origanum majorana essential oil.

Background and Objectives: This study aimed to develop a natural nanoemulsion with antibacterial and anticancer properties. Materials and Methods: The chemical composition of the Origanum majorana essential oil was investigated using GC-MS analysis. Besides, the successful loading of the essential oil in the nanoemulsion was confirmed using ATR-FTIR analysis. Moreover, nanoemulsion's anticancer, antioxidant, and antibacterial activities were investigated. Results: Terpinen-4-o1 (46.90%) was identified as the major compound in the essential oil. The nanoemulsion with a 149 ± 5 nm droplet size and zeta potential of -11 ± 1 mV was prepared. The cytotoxic effect of the nanoemulsion against A-375 human melanoma cells (IC50 = 139 µg/mL) showed significantly more potency than A-549 human lung cancer cells (IC50 = 318 µg/mL). Interestingly, growth of Staphylococcus aureus (Gram-positive) and E. coli (Gram-negative) bacteria after treatment with 4800 µg/mL of nanoemulsion were obtained at 12 ± 2 and 6 ± 1%, respectively. However, the IC50 value of nanoemulsion against E. coli (580 µg/mL) was not significantly different (P > 0.05) from S. aureus (611 µg/mL). Conclusion: A straightforward preparation method, high stability, and multi-biological effects are the main advantages of the prepared nanoemulsion. Therefore it could be considered for further investigation in vivo studies or complementary medicine.

Comparison of chitosan nanoparticles containing Lippia citriodora essential oil and citral on the induction of apoptosis in A375 melanoma cells.

BACKGROUND: Using nanoparticles containing L. citriodora EO and citral has shown potential in treating skin disorders such as melanoma. METHODS: In this study, GC‒MS was used to analyze the chemical composition of L. citriodora essential oil (EO). The ion gelation method prepared free chitosan nanoparticles and chitosan nanoparticles containing L. citriodora EO and citral. The successful loading of the EO and citral was evaluated using ATR-FTIR. The DPPH assay measured the antioxidant effect of citral, L. citriodora EO, Citral-ChiNPs, L. citriodora-ChiNPs, and Free-ChiNPs. A375 melanoma cell viability was assessed using the MTT assay. The qPCR technique was employed to evaluate the expression of apoptotic genes, and flow cytometry was used to detect apoptosis. RESULTS: This study showed that in equal concentrations, the antioxidant properties of chitosan nanoparticles containing citral were greater than those of chitosan nanoparticles containing L. citriodora. The IC50 values of chitosan nanoparticles containing citral, L. citriodora EO, and their nonformulated states were 105.6, 199.9, 136.9, and 240 µg/ml, respectively. The gene expression results showed that the ratio of the expression of the apoptosis gene to the inhibitory gene was higher than 1 in all the samples, indicating that the conditions for apoptosis were present. Flow cytometry confirmed cell apoptosis, with 93.5 ± 0.3% in chitosan nanoparticles containing citral, 80 ± 0.2% in chitosan nanoparticles containing L. citriodora EO, 63 ± 0.3 in citral, and 42.03% in L. citriodora EO-treated cells. CONCLUSION: The results showed that using the Nano form of L. citriodora and citral increased their efficiency in apoptosis pathways and their toxicity against 375 melanoma cancer cells.

Comparison effects of Ferula gummosa essential oil and Beta-pinene Alginate nanoparticles on human melanoma and breast cancer cells proliferation and apoptotic index in short term normobaric hyperoxic model.

BACKGROUND: Breast cancer is the most common cancer among women, and melanoma is the most dreadful type of skin cancer. Due to the side effects of chemotherapy drugs, the development of new herbal nano-medicines has been considered. METHODS: This study first investigated the chemical composition of Ferula gummosa essential oil using GC-MS analysis; ß-pinene, with 61.57%, was the major compound. Next, alginate nanoparticles containing ß-pinene and the essential oil with particle sizes of 174 ± 7 and 137 ± 6 nm were prepared. Meanwhile, their zeta potentials were 12.4 ± 0.7 and 28.1 ± 1 mV. Besides, the successful loading of ß-pinene and the essential oil in nanoparticles was confirmed using ATR-FTIR analysis. After that, their effects on viability and apoptotic index of human melanoma and breast cancer cells were investigated in normoxia and normobaric hyperoxia (NBO) conditions. RESULTS: The best efficacy on A-375 and MDA-MB-231 cells was achieved by alginate nanoparticles containing the EO at hyperoxic and normoxia conditions; IC50 76 and 104 µg/mL. Besides, it affected apoptosis-involved genes; as Bax/Bcl-2 ratio was higher than 1, conditions for induction of apoptosis were obtained. Higher sensitivity was observed in the A-375 cell line treated with Alg-EO in the NBO model. CONCLUSIONS: Alginate nanoparticles containing F. gummosa EO could be considered for further investigation in anticancer studies. Also, it may be expected that NBO can be a new strategy for delaying cancer progression and improving nanotherapy efficacy.

Repellent efficacy of the nanogel containing Acroptilon repens essential oil in comparison with DEET against Anopheles stephensi.

OBJECTIVE: Malaria is a vector-borne disease that causes many deaths worldwide; repellents are a practical approach to malaria prevention, especially in endemic regions. RESULTS: Gas chromatography-mass spectrometry analysis was used to identify compounds in Acroptilon repens essential oil (EO). Alpha-copaene (15.67%), α-cubenen (3.76%), caryophyllene oxide (14.00%), 1-heptadecane (5.61%), and δ-cadinene (2.84) were five major compounds. After that, the nanoemulsion containing the EO with a particle size of 46 ± 4 nm, SPAN 0.85, PDI 0.4, and zeta potential - 5.7 ± 0.4 mV was prepared. Then, it was gellified by adding CMC (carboxymethyl cellulose) to the nanoemulsion. Besides, ATR-FTIR analysis (Attenuated Total Reflection-Fourier Transform InfraRed) was used to confirm the EO's successful loading in the nanogel. Finally, the protection time and repellent activity of nanogel compared to DEET (N, N-diethyl-meta-toluamide) were investigated against Anopheles stephensi. Interestingly, the nanogel with a protection time of 310 ± 45 min was significantly more potent than DEET (160 ± 17 min). It could thus be considered for future investigation against other mosquitoes.

Effect of PCL nanofiber mats coated with chitosan microcapsules containing cinnamon essential oil for wound healing.

INTRODUCTION: Cinnamon is one of the most common spices that has been studied for its anti-inflammatory, antioxidant, and antibacterial properties in wound healing. The purpose of this study was to evaluate the effectiveness of polycaprolactone nanofiber mats coated with chitosan microcapsules loaded with cinnamon essential oil in wound healing. MATERIAL AND METHODS: For this purpose, chitosan microcapsules containing cinnamon essential oil (µCS-CiZ) were prepared by ion gelation and PCL nanofibers by electrospinning. The size of the µCS-CiZ and the morphology of nanofibers were evaluated by DLS and FESEM methods. In order to evaluate wound healing, 48 rats in 4 groups of Control, µCS-CiZ, PCL, and PCL + µCS-CiZ and were examined on days 7, 14, and 21 in terms of macroscopy (wound closure rate) and histology (edema, inflammation, vascularity, fibrotic tissue, and re-epithelialization). RESULTS: The particle size of the µCS-CiZ and the diameter of the nanofibers were estimated at about 6.33 ± 1.27 µm and 228 ± 33 nm, respectively. On day 21, both µCS-CiZ and PCL groups showed a significant decrease in wound size compared to the control group (P < 0.001). The PCL + µCS-CiZ group also showed a significant decrease compared to the µCS-CiZ (P < 0.05) and PCL groups (P < 0.05). Histological results showed further reduction of edema, inflammation, and vascularity in granulation tissue and appearance of moderate to marked fibrotic tissue in PCL + µCS-CiZ group compared with the other groups. CONCLUSION: The results of the study showed that the combined use of PCL + µCS-CiZ indicates a synergistic effect on improving wound healing.

Nanoemulsion and Nanogel Containing Cuminum cyminum L Essential Oil: Antioxidant, Anticancer, Antibacterial, and Antilarval Properties.

Cuminum cyminum L. is a widespread medicinal plant with a broad spectrum of biological activity. In the present study, the chemical structure of its essential oil was examined utilizing GC-MS analysis (gas chromatography-mass spectrometry). Then, a nanoemulsion dosage form was prepared with a droplet size and droplet size distribution (SPAN) of 121 ± 3 nm and 0.96. After that, the dosage form of the nanogel was prepared; the nanoemulsion was gelified by the addition of 3.0% carboxymethyl cellulose. In addition, the successful loading of the essential oil into the nanoemulsion and nanogel was approved by ATR-FTIR (attenuated total reflection Fourier transform infrared) analysis. The IC50 values (half maximum inhibitory concentration) of the nanoemulsion and nanogel against A-375 human melanoma cells were 369.6 (497-335) and 127.2 (77-210) µg/mL. In addition, they indicated some degrees of an antioxidant activity. Interestingly, after treatment of Pseudomonas aeruginosa with 5000 µg/mL nanogel, bacterial growth was completely (∼100%) inhibited. In addition, the growth of Staphylococcus aureus after treatment with the 5000 µg/ml nanoemulsion was decreased by 80%. In addition, nanoemulsion and nanogel LC50 values for Anopheles stephensi larvae were attained as 43.91 (31-62) and 123.9 (111-137) µg/mL. Given the natural ingredients and promising efficacy, these nanodrugs can be regarded for further research against other pathogens or mosquito larvae.

Nano-scaled emulsion and nanogel containing Mentha pulegium essential oil: cytotoxicity on human melanoma cells and effects on apoptosis regulator genes.

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.

Applications of Metallic Nanoparticles in the Skin Cancer Treatment.

Skin cancer is one of leading cancers globally, divided into two major categories including melanoma and nonmelanoma. Skin cancer is a global concern with an increasing trend, hence novel therapies are essential. The local treatment strategies play a key role in skin cancer therapy. Nanoparticles (NPs) exert potential applications in medicine with huge advantages and have the ability to overcome common chemotherapy problems. Recently, NPs have been used in nanomedicine as promising drug delivery systems. They can enhance the solubility of poorly water-soluble drugs, improve pharmacokinetic properties, modify bioavailability, and reduce drug metabolism. The high-efficient, nontoxic, low-cost, and specific cancer therapy is a promising goal, which can be achieved by the development of nanotechnology. Metallic NPs (MNPs) can act as important platforms. MNPs development seeks to enhance the therapeutic efficiency of medicines through site specificity, prevention of multidrug resistance, and effective delivery of therapeutic factors. MNPs are used as potential arms in the case of cancer recognition, such as Magnetic Resonance Imaging (MRI) and colloidal mediators for magnetic hyperthermia of cancer. The applications of MNPs in the cancer treatment studies are mostly due to their potential to carry a large dose of drug, resulting in a high concentration of anticancer drugs at the target site. Therefore, off-target toxicity and suffering side effects caused by high concentration of the drug in other parts of the body are avoided. MNPs have been applied as drug carriers for the of improvement of skin cancer treatment and drug delivery. The development of MNPs improves the results of many cancer treatments. Different types of NPs, such as inorganic and organic NPs have been investigated in vitro and in vivo for the skin cancer therapy. MNPs advantages mostly include biodegradability, electrostatic charge, good biocompatibility, high drug payload, and low toxicity. However, the use of controlled-release systems stimulated by electromagnetic waves, temperature, pH, and light improves the accumulation in tumor tissues and improves therapeutic outcomes. This study (2019-2022) is aimed at reviewing applications of MNPs in the skin cancer therapy.

Antioxidative, anticancer, and antibacterial activities of a nanogel containing Mentha spicata L. essential oil and electrospun nanofibers of polycaprolactone-hydroxypropyl methylcellulose.

BACKGROUND: As the largest organ, the skin has been frequently affected by trauma, chemical materials, toxins, bacterial pathogens, and free radicals. Recently, many attempts have been made to develop natural nanogels that, besides hydrating the skin, could also be used as antioxidant or antibacterial agents. METHODS: In this study, the chemical composition of the Mentha spicata essential oil was first investigated using GC-MS analysis. Its nanoemulsion-based nanogel was then investigated; successful loading of the essential oil in the nanogel was confirmed using FTIR analysis. Besides, nanogel's antioxidative, anticancer, and antibacterial activities were investigated. RESULTS: Carvone (37.1%), limonene (28.5%), borneol (3.9%), ß-pinene (3.3%), and pulegone (3.3%) were identified as five major compounds in the essential oil. By adding carboxymethylcellulose (3.5% w/v) to the optimal nanoemulsion containing the essential oil (droplet size of 196 ± 8 nm), it was gelified. The viscosity was fully fitted with a common non-Newtonian viscosity regression, the Carreau-Yasuda model. The antioxidant effect of the nanogel was significantly more potent than the essential oil (P < 0.001) at all examined concentrations (62.5-1000 µg/mL). Furthermore, the potency of the nanogel with an IC50 value of 55.0 µg/mL was substantially more (P < 0.001) than the essential oil (997.4 µg/mL). Also, the growth of Staphylococcus aureus and Escherichia coli after treatment with 1000 µg/mL nanogel was about 50% decreased compared to the control group. Besides, the prepared electrospun polycaprolactone-hydroxypropyl methylcellulose nanofibers mat with no cytotoxic, antioxidant, or antibacterial effects was proposed as lesion dressing after treatment with the nanogel. High potency, natural ingredients, and straightforward preparation are advantages of the prepared nanogel. Therefore, it could be considered for further consideration in vivo studies.

Nanoemulsion and Nanogel Containing Eucalyptus globulus Essential Oil; Larvicidal Activity and Antibacterial Properties.

Eucalyptus globulus essential oil (EGEO) possesses many biological effects such as antibacterial, antifungal, and insecticide properties. In the current study, the chemical composition of EGEO was first investigated using GC-MS analysis. Then, a nanoemulsion and nanogel containing EGEO (EGEO-nanoemulsion and EGEO-nanogel) were prepared. After that, the successful loading of EGEO was confirmed using ATR-FTIR analysis. EGEO-nanoemulsion and EGEO-nanogel with LC50 values of 27 and 32 µg/mL showed promising efficacies against Anopheles stephensi larvae. Besides, the efficacy of EGEO-nanogel (IC50 187 µg/mL) was significantly more potent than EGEO-nanoemulsion (IC50 3732 µg/mL) against Staphylococcus aureus. However, no significant difference was observed in the efficacy of EGEO-nanoemulsion and EGEO-nanogel against Pseudomonas aeruginosa. Natural components, straightforward preparation, and proper efficacy are some of the advantages of EGEO-nanogel; it could be considered for further consideration against other pathogens and mosquito larvae.

Nanoemulsion and nanogel containing Artemisia dracunculus essential oil; larvicidal effect and antibacterial activity.

OBJECTIVE: Microbial infections and mosquito-borne diseases such as malaria, with 627 k deaths in 2020, are still major public health challenges. RESULTS: This study prepared nanoemulsion and nanogel containing Artemisia dracunculus essential oil. ATR-FTIR analysis (Attenuated Total Reflection-Fourier Transform InfraRed) confirmed the successful loading of the essential oil in nanoemulsion and nanogel. LC50 values (Lethal Concentration 50%) of nanogel and nanoemulsion against Anopheles stephensi larvae were obtained as 6.68 (2-19 µg/mL) and 13.53 (7-25 µg/mL). Besides, the growth of Staphylococcus aureus after treatment with 5000 µg/mL nanogel and nanoemulsion was reduced by ~ 70%. However, about 20% growth of Pseudomonas aeruginosa was reduced at this dose. Considering the proper efficacy of the nanogel as a larvicide and proper antibacterial effect against S. aureus, it could be considered for further investigations against other mosquitoes' larvae and gram-positive bacteria.

A Nanoliposomal Gel Containing Cinnamomum zeylanicum Essential Oil with Effective Repellent against the Main Malaria Vector Anopheles stephensi.

Malaria is the most important vector-borne disease; however, mosquito repellents are still a practical approach for controlling malaria, especially in endemic regions. Due to the side effects of synthetic repellents such as N, N-diethyl-meta-toluamide (DEET), the development of natural repellents has received much attention. In this study, nanoliposomes containing 0.5 and 2.5% w/v Cinnamomum zeylanicum essential oil were firstly prepared with particle sizes of 119 ± 6 and 195 ± 9 nm. Their morphologies and loading of the essential oil in the particles were then investigated using transmission electron microscopy (TEM) and attenuated total reflection-Fourier transform infrared (ATR-FTIR) analyses. The nanoliposomes were finally jellified to increase their viscosity and facilitate topical usage. The complete protection time of the nanoliposomal gel containing 2.5% C. zeylanicum essential oil was significantly longer than that of 2.5% DEET against Anopheles stephensi: 303 ± 10 > 242 ± 12 min, p < 0.001. Moreover, the prepared nanoformulation was stable for at least six months at 4 and 26°C. Therefore, the prepared prototype could be considered a natural repellent against the main malaria mosquito vector in field conditions. In addition, it is suggested to be investigated against other important factors mosquitoes.

High anticancer efficacy of solid lipid nanoparticles containing Zataria multiflora essential oil against breast cancer and melanoma cell lines.

BACKGROUND: The cancer burden is rising rapidly worldwide, and it annually causes about 8.8 million deaths worldwide. Due to chemical drugs' side effects and the emergence of resistance, the development of new green drugs has received much attention. We aimed to investigate whether solid-lipid nanoparticles containing essential oil of Zataria multiflora (ZMSLN) enhanced the anticancer efficacy of the essential oil against breast cancer (MDA-MB-468) and melanoma (A-375) cells. RESULTS: ZMSLN was prepared by the high-pressure homogenizer method; particle size 176 ± 8 nm, polydispersity index 0.22 ± 0.1, entrapment efficiency 67 ± 5%. The essential oil showed a dose-dependent antiproliferative effect on MDA-MB-468 and A-375 cells at all examined concentrations (75, 150, 300, 600, and 1200 µg/mL). Interestingly, after treating both cells with 75 µg/mL of ZMSLN, their viabilities were reduced to under 13%. CONCLUSION: The finding showed that ZMSLN had a distinct antiproliferative efficacy; it could thus be considered a green anticancer candidate for further in vivo and in vivo studies.

Improving the oxidative stability of virgin olive oil using microformulated vitamin-C.

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.

Chitosan nanoparticles containing limonene and limonene-rich essential oils: potential phytotherapy agents for the treatment of melanoma and breast cancers.

BACKGROUND: Melanoma and breast cancers are two common cancers worldwide. Due to the side effects of chemotherapy drugs and the occurring resistance against them, the development of green drugs has been received more attention. METHODS: The anticancer effects of three essential oils from the Citrus family and their identified major constituents (limonene) were first investigated against melanoma and breast cancer cell lines (A-375 and MDA-MB-468). By preparing chitosan nanoparticles containing them, an attempt was then made to improve their effectiveness. RESULTS: Chitosan nanoparticles containing Citrus sinensis and Citrus limon essential oils with IC50s of 0.03 and 0.124 µg/mL on A-375 cells, and 23.65 and 40.32 µg/mL on MDA-MB-468 showed distinct anticancer efficacies. CONCLUSION: The prepared formulations could thus be considered as green anticancer agents in complementary medicine and therapies.

A nanoemulsion-based nanogel of Citrus limon essential oil with leishmanicidal activity against Leishmania tropica and Leishmania major.

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 carbomer 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, Carreau-Yasuda. Interestingly, CLNgel at a concentration of 80 µg/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.

Preparation of nanoemulsion of Cinnamomum zeylanicum oil and evaluation of its larvicidal activity against a main malaria vector Anopheles stephensi.

PURPOSE: There is a growing need to use green and efficient larvicidal as alternatives for conventional chemicals in vector control programs. Nanotechnology has provided a promising approach for research and development of new larvicides. Larvicidal potential of a nanoemulsion of Cinnamomum zeylanicum essential oil reports against Anopheles stephensi. METHODS: The nanoemulsion of was formulated in various ratios comprising of C. zeylanicum oil, tween 80, span 20 and water by stirrer. It was characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). All components of C. zeylanicum essential oil were identified by GC-MS analysis. The larvicidal potential of the oil and its nanoformulation were evaluated against larvae of An. stephensi. The stability and durability of nanoemulsion was observed over a period of time. RESULTS: Sixty one components in the oil were identified, cinnamaldehyde (56.803%) was the main component. The LC90 and LC50 values of C. zeylanicum essential oil were calculated as 49 ppm and 37 ppm, respectively. The nanoemulsion droplets were found spherical in shape. It was able to kill 100% of larvae in up to 3 days. It was stable after dilution and increased its larvicidal activity up to 32% compared with the essential oil. CONCLUSIONS: A novel larvicide based on nanotechnology introduced. This experiment clearly showed increasing larvicidal activity and residual effect of the nanoformulation in comparison with the bulk essential oil. It could be concluded that this nanoemulsion may be considered as safe larvicide and should be subject of more research in this field.

Solid-lipid nanoparticles (SLN)s containing Zataria multiflora essential oil with no-cytotoxicity and potent repellent activity against Anopheles stephensi.

Malaria is still a global health concern with more than 400,000 death annually. Personal protection using mosquitoes' repellent is an effective prevention strategy, especially in endemic areas. The toxic effects of synthetics repellents and their adverse effects on fabricated goods have made the development of green repellent critical. In this study, ingredients of Zataria multiflora essential oil (ZMEO) were identified using GC-MS analysis. Solid-lipid nanoparticles containing ZMEO (1%) were prepared (SLN-ZMEO) using the high-pressure homogenizer method. The repellent activity of ZMEO and SLN-ZMEO was investigated using Klun and Debboun method and compared together. Besides, their cytotoxicity on a human skin normal cell line (HFFF2) was evaluated. Five major components of ZMEO were carvacrol (27.05%), thymol (26.452%), γ-terpinene (15.144%), o-cymene (13.584%), and α-pinene (9.483%). The SLN-ZMEO showed a spherical shape with a particle size of 134 ± 7 nm. Moreover, their polydispersity index (PDI), zeta potential and entrapment efficiency were determined as 0.24 ± 0.1, - 9.82 ± 0.95 mV and 64.6 ± 3.8%, respectively. Interestingly, the protection time of nanoformulation (93 ± 5 min) was three times longer than that of the non-formulated essential oil (29 ± 2 min). Interestingly, both samples did not show cytotoxicity on HFFF2. Therefore, the prepared nanoformulation can be used as a green and potent repellent.