Capsicum annuum Oleoresin Nanoemulgel - Design Characterization and In vitro Investigation of Anticancer and Antimicrobial Activities.

BACKGROUND: The use of naturally occurring bioactive materials is getting great attention owing to their safety and environmental properties. Oily compounds, known as oleoresins, are expected to provide an important source for the natural products industry aiming to develop novel treatments for skin conditions. In this work, Capsicum annuum oleoresin nanoemulgel formulations have been prepared and investigated for their antibacterial and anticancer properties. METHODOLOGY: Several C. annuum oleoresin nanoemulgel formulations were prepared by incorporating a Carbopol 940 gel in a self-nanoemulsifying nanoemulsion consisting of C. annuum, tween 80, and span 80. The systems were characterized for particle size, polydispersity index (PDI), zeta potential, and rheology. The in vitro antimicrobial and cytotoxic activities of the optimum formulation were evaluated. RESULTS: The selected formulation is composed of 40% tween, 10% span 80, and 40% C. annuum oleoresin. This formulation produced a stable nanoemulsion with a narrow PDI value of 0.179 ± 0.08 and a droplet size of 104.0 ± 2.6 nm. Results of the in vitro antimicrobial studies indicated high potency of the systems against methicillin-resistant Staphylococcus aureus (MRSA) (zone of inhibition of 29 ± 1.9 mm), E. coli (33 ± 0.9 mm), K. pneumonia (30 ± 1.4 mm), and C. albicans (21 ± 1.5 mm), as compared to the reference antibiotic, ampicillin (18 ± 1.4 mm against K. pneumonia), and antifungal agent, fluconazole (12 ± 0.1 mm against C. albicans). Furthermore, cytotoxicity results, expressed as IC50 values, revealed that the oleoresin and its nanoemulgel had the best effects against the HepG2 cell line (IC50 value of 79.43 µg/mL for the nanoemulgel) and MCF7 (IC50 value of 57.54 µg/mL), and the most potent effect was found against 3T3 (IC50 value of 45.7 µg/m- L). On the other side, the system did not substantially exhibit activity against By-61 and Hela. CONCLUSION: C. annuum oleoresin and its nanoemulgel can be considered valuable sources for the discovery of new antibacterial, antifungal, and anticancer compounds in the pharmaceutical industry, especially due to their potent activity against various cancer cell lines as well as bacterial and fungal strains.

Assessment of anticancer, antimicrobial, antidiabetic, anti-obesity and antioxidant activity of Ocimum Basilicum seeds essential oil from Palestine.

BACKGROUND: Many modern pharmaceutical researchers continue to focus on the discovery and evaluation of natural compounds for possible therapies for obesity, diabetes, infections, cancer, and oxidative stress. Extraction of Ocimum basilicum seed essential oil and evaluation of its antioxidant, anti-obesity, antidiabetic, antibacterial, and cytotoxic activities were the goals of the current study. METHOD: O. basilicum seed essential oil was extracted and evaluated for its anticancer, antimicrobial, antioxidant, anti-obesity, and anti-diabetic properties utilizing standard biomedical assays. RESULTS: O. basilicum seed essential oil showed good anticancer activity against Hep3B (IC50 56.23 ± 1.32 µg/ml) and MCF-7 (80.35 ± 1.17 µg/ml) when compared with the positive control, Doxorubicin. In addition, the essential oil showed potent antibacterial (against Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Proteus mirabilis, and Pseudomonas aeruginosa) and antifungal (against Candida albicans) activities. Moreover, as for the anti-amylase test, IC50 was 74.13 ± 1.1 µg/ml, a potent effect compared with the IC50 of acarbose, which was 28.10 ± 0.7 µg/ml. On the other hand, for the anti-lipase test, the IC50 was 112.20 ± 0.7 µg/ml a moderate effect compared with the IC50 of orlistat, which was 12.30 ± 0.8 µg/ml. Finally, the oil had a potent antioxidant effect with an IC50 of 23.44 ± 0.9 µg/ml compared with trolox (IC50 was 2.7 ± 0.5 µg/ml). CONCLUSION: This study has provided initial data that supports the importance of O. basilcum essential oil in traditional medicine. The extracted oil not only exhibited significant anticancer, antimicrobial, and antioxidant properties but also antidiabetic and anti-obesity effects, which provided a foundation for future research.

Antibacterial and Anti-Acne Activity of Benzoyl Peroxide Nanoparticles Incorporated in Lemongrass Oil Nanoemulgel.

PURPOSE: The goal of this study was to make Benzoyl Peroxide (BPO) nanoemulgel to improve its ability to kill bacteria. BPO has trouble getting into the skin, being absorbed by the skin, staying stable, and being spread out. METHODS: A BPO nanoemulgel formulation was prepared by combining BPO nanoemulsion with Carbopol hydrogel. The drug was tested for solubility in various oils and surfactants in order to select the best oil and surfactant for the drug, and then the drug nanoemulsion formulation was prepared using a self-nano-emulsifying technique with Tween 80, Span 80, and lemongrass oil. The drug nanoemulgel was looked at in terms of its particle size, polydispersity index (PDI), rheological behavior, drug release, and antimicrobial activity. RESULTS: Based on the solubility test results, lemongrass oil was the best solubilizing oil for drugs, while Tween 80 and Span 80 demonstrated the highest solubilizing ability for drugs among the surfactants. The optimum self-nano-emulsifying formulation had particle sizes of less than 200 nm and a PDI of close to zero. The results showed that incorporating the SNEDDS formulation of the drug with Carbopol at various concentrations did not cause a significant change in the particle size and PDI of the drug. The zeta potential results for drug nanoemulgel were negative, with more than 30 mV. All nanoemulgel formulations exhibited pseudo-plastic behavior, with 0.4% Carbopol exhibiting the highest release pattern. The drug nanoemulgel formulation worked better against bacteria and acne than the product on the market. CONCLUSION: Nanoemulgel is a promising way to deliver BPO because it makes the drug more stable and increases its ability to kill bacteria.

Synthesis of novel isoxazole-carboxamide derivatives as promising agents for melanoma and targeted nano-emulgel conjugate for improved cellular permeability.

BACKGROUND: Cancer is one of the most dangerous and widespread diseases in the world today and it has risen to the position of the leading cause of death around the globe in the last few decades. Due to the inherent resistance of many types of cancer to conventional radiotherapy and chemotherapy, it is vital to develop innovative anticancer medications. Recently, a strategy based on nanotechnology has been used to improve the effectiveness of both old and new cancer drugs. OBJECTIVES: The present study aimed to design and synthesize a series of phenyl-isoxazole-Carboxamide derivatives, evaluate their anticancer properties, and improve the permeability of potent compounds into cancer cells by using a nano-emulgel strategy. METHODS: The coupling reaction of aniline derivatives and isoxazole-Carboxylic acid was used to synthesize a series of isoxazole-Carboxamide derivatives. IR, HRMS, 1H-NMR, and 13C-NMR spectroscopy techniques, characterized all the synthesized compounds. The in-vitro cytotoxic evaluation was performed by using the MTS assay against seven cancer cell lines, including hepatocellular carcinoma (Hep3B and HepG2), cervical adenocarcinoma (HeLa), breast carcinoma (MCF-7), melanoma (B16F1), colorectal adenocarcinoma (Caco-2), and colon adenocarcinoma (Colo205), as well as human hepatic stellate (LX-2) in addition to the normal cell line (Hek293T). A nano-emulgel was developed for the most potent compound, using a self-emulsifying technique. RESULTS: All synthesized compounds were found to have potent to moderate activities against B16F1, Colo205, and HepG2 cancer cell lines. The results revealed that the 2a compound has broad spectrum activity against B16F1, Colo205, HepG2, and HeLa cancer cell lines with an IC50 range of 7.55-40.85 µM. Moreover, compound 2e was the most active compound against B16F1 with an IC50 of 0.079 µM compared with Dox (IC50 = 0.056 µM). Nanoemulgel was used to increase the potency of the 2e molecule against this cancer cell line, and the IC50 was reduced to 0.039 µM. The antifibrotic activities were investigated against the LX-2 cell line, and it was found that our synthesized molecules showed better antifibrotic activities at 1 µM than 5-FU, and the cell viability values were 67 and 95%, respectively. CONCLUSION: This study suggests that a 2e nano-formalized compound is a potential and promising anti-melanoma agent.

Antidiabetic, antioxidant, and anti-obesity effects of phenylthio-ethyl benzoate derivatives, and molecular docking study regarding α-amylase enzyme.

In addition to their wide therapeutic application, benzoates and benzoic acid derivatives are the most commonly utilized food preservatives. The purpose of this study was to estimate the antioxidant, anti-diabetic, and anti-obesity activities of four 2-(phenylthio)-ethyl benzoate derivatives utilizing standard biomedical assays. The results revealed that the 2a compound has potent antidiabetic activity through the inhibition of α-amylase and α-glycosidase with IC50 doses of 3.57 ± 1.08 and 10.09 ± 0.70 µg/ml, respectively, compared with the positive control acarbose (IC50 = 6.47 and 44.79 µg/ml), respectively. In addition, by utilizing the ß-carotene linoleic acid and DPPH methods, the 2a compound showed the highest antioxidant activity compared with positive controls. Moreover, the 2a compound showed potential anti-lipase activity with an IC50 dose of 107.95 ± 1.88 µg/ml compared to orlistat (IC50 = 25.01 ± 0.78 µg/ml). A molecular docking study was used to understand the interactions between four derivatives of (2-(phenylthio)-ethyl benzoate with α-amylase binding pocket. The present study concludes that the 2a compound could be exploited for further antidiabetic, antioxidant, and anti-obesity preclinical and clinical tests and design suitable pharmaceutical forms to treat these global health problems.

Development of Coriandrum sativum Oil Nanoemulgel and Evaluation of Its Antimicrobial and Anticancer Activity.

This study is aimed at developing coriander oil into a nanoemulgel and evaluating its antimicrobial and anticancer effects. Coriander (Coriandrum sativum) oil was developed into a nanoemulgel by using a self-nanoemulsifying technique with Tween 80 and Span 80. Hydrogel material (Carbopol 940) was then incorporated into the nanoemulsion and mixed well. After this, we evaluated the particle size, polydispersity index (PDI), rheology, antimicrobial effect, and cytotoxic activity. The nanoemulsion had a PDI of 0.188 and a particle size of 165.72 nm. Interesting results were obtained with the nanoemulgel against different types of bacteria, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 2.3 µg/ml, 3.75 µg/ml, and 6.5 µg/ml, respectively. In addition, the half-maximal inhibitory concentration (IC50) of the nanoemulgel when applying it to human breast cancer cells (MCF-7), hepatocellular carcinoma cells (Hep3B), and human cervical epithelioid carcinoma cells (HeLa) was 28.84 µg/ml, 28.18 µg/ml, and 24.54 µg/ml, respectively, which proves that the nanoemulgel has anticancer effects. The development of C. sativum oil into a nanoemulgel by using a self-nanoemulsifying technique showed a bioactive property better than that in crude oil. Therefore, simple nanotechnology techniques are a promising step in the preparation of pharmaceutical dosage forms.

Biological evaluation of Safrole oil and Safrole oil Nanoemulgel as antioxidant, antidiabetic, antibacterial, antifungal and anticancer.

BACKGROUND: Safrole is a natural compound extracted from various plants, and has shown various biological activities. The current study aimed to investigate the antioxidant, antidiabetic, antimicrobial, and anticancer activity of safrole oil and to study the influence of safrole nanoemulgel on these activities. METHODS: The antioxidant and antidiabetic in-vitro assays were conducted using standard biomedical methods. The safrole oil nanoemulgel was developed using a self-emulsifying technique. Then the antimicrobial activity of the safrole oil and safrole nanoemulgel were performed on different microbial species, and cytotoxicity was determined against Hep3B cancer cell lines using the MTS assay. RESULTS: Safrole oil showed moderate antioxidant activity compared with standard Trolox, with IC50 value 50.28 ± 0.44 and 1.55 ± 0.32 µg/ml, respectively. Moreover, it had potent α-amylase inhibitory activity (IC50 11.36 ± 0.67 µg/ml) compared with Acarbose (IC50 value 5.88 ± 0.63). The safrole nanoemulgel had pseudo-plastic behaviour, droplet sizes below 200 nm, a polydispersity index (PDI) below 0.3, and a zeta potential of less than - 30 mV. Safrole oil has potential antimicrobial and anticancer activities, and these activities were improved with safrole nanoemulgel. CONCLUSION: The safrole oil may be applied for the prevention and treatment of oxidative stress, diabetes, different microbial species and cancer, and these activities could be improved by nano-carriers.

Synthesis and Biological Evaluation of Novel Isoxazole-Amide Analogues as Anticancer and Antioxidant Agents.

Cancer now is one of the leading causes of mortality in the world. There has been a lot of effort to discover new anticarcinogenic agents that allow treatment with fewer side effects. A series of isoxazole-carboxamide derivatives (2a-2g) were synthesised and evaluated for their cytotoxic activity against breast (MCF-7), cervical (HeLa), and liver (Hep3B) cancer cell lines and their antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The results showed that 2d and 2e were the most active compounds against Hep3B cells, with a half-maximal inhibitory concentration (IC50) of around 23 µg/ml; 2d showed the highest activity against HeLa cells, with an IC50 15.48 µg/ml. However, 2a had the lowest IC50 (39.80 µg/ml) against MCF-7 cells. By contrast, compound 2g was inactive against all cancer cell lines, with IC50 values >400 µg/ml. Both 2d and 2e reduced Hep3B secretion of alpha-fetoprotein (to 1829.33 ± 65.91 ng/ml and 1758.66 ± 54.04 ng/ml, respectively). Furthermore, in cell cycle analysis, 2d and 2e induced a delay in the G2/M phase of 18.07%, which is similar to the doxorubicin positive control. Moreover, 2d and 2e reduced the necrosis rate of Hep3B threefold and instead shifted the cells to apoptosis. Our results indicate that 2d and 2e have potent and promising anticancer activity. However, compound 2a was the most active as antioxidant agent (IC50 = 7.8 ± 1.21 µg/ml) compared with Trolox as a positive control (IC50 2.75 µg/ml).

Formulation and In Vitro and In Vivo Assessment of Natural Emulgel Containing Lemongrass Essential Oil.

This study aimed to develop a topical emulgel formulation from olive oil and lemongrass (LG) extracts and to evaluate its in vitro and in vivo (sensorial) properties in addition to its sun protection factor (SPF) value. The primary emulsion and the gel were prepared separately, and then they were levigated together to formulate the emulgel. The produced emulgel was evaluated for its physical appearance, pH, spreadability, and stability. The SPF value of emulgel was evaluated by applying the Mansur equation. Moreover, an in vivo sensorial assessment was conducted on the emulgel through a crossover study by including 20 volunteers. The results confirm good stability for emulgel formulations because there was no significant change in the pH value, no micelle inversion, or phase separation detected. The emulgel recorded a moderate SPF value (5.5) which can be useful for daily use, especially in tanned skin subjects. Moreover, the sensorial assessment of LG and blank emulgels showed a significant change in the cooling effect, odor, and smoothness and add some kind of moisture. In fact, there was a significant difference in overall properties between the two formulations where the p-value was less than 0.05. It is concluded the emulgel formulation containing LG and olive oil could be beneficial in terms of applicability and stability and can be easily formulated in pharmaceutical facilities. Besides, it would be useful for daily use because of the overall suitable properties, especially odor, feel, and SPF value.

Development and Antimicrobial Evaluation of Eruca Sativa Oil Nanoemulgel with Determination of the Oil Antioxidant, Sun Protection Factor and Elastase Inhibition.

OBJECTIVES: This project aims to develop a bio-natural nano-product with Cosmeceutical and pharmaceutical applications. METHODS: E. sativa oil was evaluated for its anti-oxidant, sun protection factor and elastase inhibition. Then, nanoemulgel formulations were prepared for E. sativa oil through the combination of nanoemulsion with hydrogel. E. sativa nanoemulsion formulations were prepared by the help of a selfemulsification technique. After this, the optimum formulation was mixed with Carbopol to produce the nanoemulgel. Anti-bacterial and anti-fungal activities were evaluated. RESULTS: Nanoemulsion occurred when the size of the droplets was 195.29 nm with the lowest polydispersibility index 0.207. The results of antioxidant, anti-elastase and SPF activities for E. sativa oil were 2.10 µg/ml, 25.1 µg/ml and an SPF value of 5.57, respectively. In addition, in the anti-bacterial test for Staphylococcus aureus, it was found that nanoemulgel has an inhibition zone of 2.1 cm in diameter. According to the MRSA, the inhibition zone was 1.5 cm. CONCLUSION: E. Sativa oil could be a promising candidate in cosmeceutical and pharmaceutical preparations.

Antibacterial Activity of Fusidic Acid and Sodium Fusidate Nanoparticles Incorporated in Pine Oil Nanoemulgel.

PURPOSE: Fusidic acid (FA) and sodium fusidate (SF) have problems in their skin penetration and stability resulting in a reduction in their potency; therefore, the objective of this study was to develop FA and SF nanoemulgels to improve the antibacterial activity of the drugs. METHODS: FA and SF nanoemulgel formulations were prepared by the incorporation of FA and SF nanoemulsions with Carbopol hydrogel. First, the drugs were screened for their solubility in different oils and surfactants to choose the suitable oil and surfactants for the drugs, and then the drug nanoemulsion formulations were prepared by a self-nanoemulsifying technique using Tween 80, Span 20 and pine oil. The drug nanoemulgels were evaluated for their particle size, polydispersity index (PDI), rheological behaviour, drug release and anti-microbial activity. RESULTS: Based on the solubility test, pine oil was the best solubilising oil for both drugs, Tween 80 and Span 20 showed the highest solubilising ability for both the drugs among the surfactants; therefore, they were chosen as surfactant and co-surfactant, respectively. The optimum self-nanoemulsifying formulations showed a particle size for fusidic acid and Sodium fusidate of 140.58 nm and 151.86 nm respectively, and both showed a low PDI below 0.3. After incorporating both drug SNEDDS formulations with Carbopol at different concentrations, the results of the drugs particle size and PDI showed no significant difference. The zeta potential results for both drugs nanoemulgels showed a negative potential with more than 30 mV. All nanoemulgel formulations showed pseudo-plastic behaviour with the highest release pattern at 0.4% Carbopol. The antibacterial activity of both drug nanoemulgel formulations showed superiority over the market product. CONCLUSION: Nanoemulgel is a promising delivery system for FA and SF that helps in improving the stability and antibacterial activities of the drugs.

Influence of sonication and in vitro evaluation of nifedipine self-nanoemulsifying drug delivery system

In order to develop a self-nanoemulsifying system, three components, olive oil, Tween 80, and Capmul, were used to construct a ternary phase diagram that helped to find the optimum formulation, which was loaded with nifedipine. The effect of sonication on drug loading was also evaluated. After that, measurement of the droplet size, size distribution, zeta potential, and scanning electron microscopy were conducted for evaluation and characterisation of the formulations. The phase diagram of four formulations showed nanosizes below 200 nm; however, only one was selected to be loaded with nifedipine. The selected formulation had the lowest droplet size of 98 nm and size distribution 0.192, and was composed of 48% Tween 80, 32% Capmul, and 20% olive oil. The nifedipine self-nanoemulsifying drug delivery system (SNEDDS) showed a significant change in the particle size (97 nm) and size distribution (0.257) after sonication. Its zeta potential was -32.3 mV indicating good stability. The SEM photographs of nifedipine showed particles with spherical shape and smooth surface. Finally, a self-nanoemulsifying formulation containing nifedipine, loaded in olive oil, was successfully prepared by mixing the oil with various types of surfactants and co-surfactants. A significant nifedipine self-nanoemulsifying system was developed and significantly improved accordingly.

A Review on the Cosmeceutical and External Applications of Nigella sativa.

It is estimated by the World Health Organization (WHO) that most of the world's population depends on herbal medicine for their health care. Nigella sativa (N. sativa), also known as black-caraway and as "Kalonji," is a well-known seed all over the world. It is one of the most common medicinal plants worldwide and contains many useful chemical constituents that we can find in its fixed oil, such as thymoquinone, thymohydroquinone, dithymoquinone, thymol, nigellicine, carvacrol, nigellimine, nigellicine, nigellidine, and alpha-hederin. Due to these numerous important ingredients it was found that it affects different areas of our body and has many pharmacological effects as antibacterial, antiviral, anti-inflammatory, and wound healing effect and also for acne vulgaris, skin cancer, pigmentation, and many cosmeceutical applications. Based on the folklore usage of N. sativa seeds and oil, they are used in various systems of food and medicines. The aim of this article is to provide a detailed survey of the literature of cosmeceutical and external applications of N. sativa which is expected to stimulate further studies on this subject.

The preparation and evaluation of self-nanoemulsifying systems containing Swietenia oil and an examination of its anti-inflammatory effects.

There is an increasing trend among pharmaceutical industries to use natural bioactive materials as medicinal agents and to use new technologies such as self-nanoemulsifying systems. The solubility and bioavailability of poorly soluble drugs can be enhanced by self-nanoemulsifying systems. Swietenia oil is frequently used because of its antimicrobial, antimutagenic, and anticancer bioactive medical properties. This study was conducted to develop self-nanoemulsifying systems for Swietenia oil that will enhance the anti-inflammatory activity of the oil. The self-emulsifying systems developed for Swietenia oil in this study were constructed using ternary phase diagrams and contained the nonionic surfactants Labrasol(®), Tween 20, Capmul(®), and Labrafil(®). The effect of these surfactants on the formulation was examined. The mean droplet size of Swietenia oil as well as their distribution, appearance, viscosity, and spreading times were studied to find the optimum formula, which contained droplets that were less than 200 nm. The next step was to test the anti-inflammatory properties of the optimum formula using a carrageenan-induced rat paw edema test. The results from this test were compared to the oil solution. Different oil/surfactants mixtures had various emulsification properties that were related to the size of their droplets. Tween 20 is a good surfactant to use in self-emulsifying systems because it produces droplets of nano-size. Mixtures of Capmul/Labrasol at a ratio of 2:1 and Labrafil/Tween 20 at a ratio of 1:2 were able to produce self-nanoemulsifying formulations containing Swietenia oil concentrations that ranged from 20%-50%. Nanoemulsion occurred when the size of the droplets fell below 200 nm with low size distribution (<0.3) after being gently mixed with water. It was found that the hydrophilic/lipophilic balance value affected the ternary phase diagram behavior of Swietenia oil and surfactants. In addition, the anti-inflammatory properties of Swietenia oil were greater in the self-nanoemulsifying systems than in the oil solution.