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Authors = Rawaf Alenazy ORCID = 0000-0002-8954-7250

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23 pages, 2694 KiB  
Article
Antioxidant and Antibacterial Activities and Phytochemical Analysis of Olea europaea subsp. laperrinei Leaves Extracts
by Souad Lahcene, Idir Moualek, Karim Bariz, Elias Benramdane, Rawaf Alenazy, Mohammed Alqasmi, Fawaz M. Almufarriji, Mohammed Thabet, Ghaith Fallata, Nasser Alqurainy, Bilal Saoudi, Nassima Sadoun, Lamia Trabelsi and Karim Houali
Processes 2025, 13(4), 1113; https://doi.org/10.3390/pr13041113 - 7 Apr 2025
Cited by 1 | Viewed by 751
Abstract
Olea europaea subsp. laperrinei, endemic to the central Sahara in Algeria, Niger, and Sudan, is recognized for its therapeutic and nutritional benefits, notably its antioxidant and antibacterial properties. This study investigates the phytochemical composition and biological activities of its leaf extracts obtained [...] Read more.
Olea europaea subsp. laperrinei, endemic to the central Sahara in Algeria, Niger, and Sudan, is recognized for its therapeutic and nutritional benefits, notably its antioxidant and antibacterial properties. This study investigates the phytochemical composition and biological activities of its leaf extracts obtained via aqueous and ethanolic extraction. Total phenols, flavonoids, and tannins were quantified by UV–visible spectrophotometry, while individual phenolic compounds were identified by HPLC-UV. Antioxidant capacity was measured using DPPH radical scavenging, hydrogen peroxide neutralization, and β-carotene bleaching assays. Antibacterial activity was evaluated against nine bacterial strains. The ethanolic extract exhibited higher total phenol (134.72 ± 9.25 mg GAE/g VP) and flavonoid (26.08 ± 1.57 mg QE/g VP) contents, while tannin levels were similar in both extracts. Twenty-seven phenolic compounds, including oleuropein, hydroxytyrosol, rutin, and quercetin, were identified. The ethanolic extract showed superior antioxidant capacity, with an EC50 of 7.48 ± 0.39 µg/mL (DPPH) and IC50 values of 214.04 ± 2.89 µg/mL (H2O2) and 185.63 ± 3.84 µg/mL (β-carotene). Both extracts exhibited antibacterial effects, with inhibition zones up to 23.33 ± 0.76 mm and MIC values as low as 0.78 mg/mL. These findings highlight the potential of Laperrine olive leaves as natural antioxidant and antibacterial agents. Full article
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16 pages, 971 KiB  
Article
Ventriculoperitoneal Shunt Infections: Causative Pathogens and Associated Outcomes from Multiple Hospitals in Saudi Arabia
by Mohammed Alqasmi, Yousif A. Kariri, Rawaf Alenazy, Mohammed Thabet, Ghaith Fallata and Nasser Alqurainy
J. Clin. Med. 2025, 14(6), 2006; https://doi.org/10.3390/jcm14062006 - 16 Mar 2025
Viewed by 941
Abstract
Background: Ventriculoperitoneal shunting (VPS) is the primary treatment for hydrocephalus, significantly improving patients’ outcomes. However, it is marred by high failure rates due to infections, which account for a third of these malfunctions and escalate morbidity, mortality, and healthcare costs. Method: This study [...] Read more.
Background: Ventriculoperitoneal shunting (VPS) is the primary treatment for hydrocephalus, significantly improving patients’ outcomes. However, it is marred by high failure rates due to infections, which account for a third of these malfunctions and escalate morbidity, mortality, and healthcare costs. Method: This study focused on evaluating VPS infection rates, pathogens, their resistance patterns, and the impact on clinical outcomes using retrospective data from multiple hospitals in Saudi Arabia. It included data from hydrocephalus patients who underwent VPS and only considered positive cultures that were confirmed from CSF or shunt tip samples. Results: This study excluded patients with prior infections before VPS placement or those treated with alternatives to VPS. Out of 317 patients who met the inclusion criteria, the analysis revealed that 23 patients (7.26%) suffered from VPS infections, mostly within the first two weeks post-surgery (58.06% of cases), with a significant discrepancy in infection rates between hospitals. Infections predominantly involved Gram-positive bacteria (58.08%), especially coagulase-negative staphylococci and Staphylococcus aureus (25.81% and 12.90%, respectively). There was also a substantial presence of Gram-negative bacteria and fungi, accounting for 35.46% and 6.46%, respectively. Despite general antibiotic susceptibility, resistance was significant in certain cases, including multidrug-resistant isolates like Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter ursingii. Importantly, patients with VPS infections had a tenfold increase in the length of hospital stay (70.84 days, SD ± 139.5) compared to non-infected patients (7.69 days, SD ± 20.72), indicating high morbidity and associated treatment costs. Conclusions: Our results emphasize the importance of better VPS infection control and standardized hospital protocols to decrease the incidence of VPS-related infections, both in Saudi Arabia and globally. Full article
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21 pages, 4418 KiB  
Article
Olive Tree Twigs as an Attractive Green Source of Antioxidant and Antibiofilm Biomolecules
by Samia Dermeche, Kahina Mezoued, Hinda Naib, Nassima Senani, Thinina Afif Chaouche, Rawaf Alenazy, Mohammed Sanad Alhussaini, Alyahya Abdulrahman A. I., Mohammed Alqasmi, Fawaz M. Almufarriji, Fahad Mohammed Alturaiki, Samia Bedouhene, El-hafid Nabti, Lamia Trabelsi and Karim Houali
Processes 2025, 13(2), 559; https://doi.org/10.3390/pr13020559 - 17 Feb 2025
Cited by 1 | Viewed by 752
Abstract
Biofilms represent complex three-dimensional microbial communities that can harbor strains highly resistant to antimicrobial agents. These structures, which form on both biotic and abiotic surfaces, are associated with food spoilage and increased complications in hospitalized patients. Consequently, there is significant interest in developing [...] Read more.
Biofilms represent complex three-dimensional microbial communities that can harbor strains highly resistant to antimicrobial agents. These structures, which form on both biotic and abiotic surfaces, are associated with food spoilage and increased complications in hospitalized patients. Consequently, there is significant interest in developing novel biofilm and infection control strategies, particularly those focusing on natural molecules with dual antimicrobial and antibiofilm properties. In this study, olive tree twigs from three varieties of Olea europea chemlal (CH), Azeradj (AZ), and wild-type Olea europaea sylvestris (W) were collected from the Kabylia region in Algeria. The samples underwent systematic extraction and were evaluated for their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, antimicrobial properties via disk diffusion assay, minimum inhibitory concentration (MIC), and antibiofilm capabilities. Results demonstrated that olive tree twig extracts exhibited substantial antioxidant activity and significant antibacterial and antibiofilm potential. The antioxidant activity, measured through DPPH radical scavenging, showed IC50 values ranging from 38.12 ± 1.52 µg/mL to 148.7 ± 1.23 µg/mL. When tested against six pathogenic bacterial strains, including both ATCC reference strains and milk isolates, the MIC values ranged from 1.18 mg/mL to 4.71 mg/mL. Notably, sub-inhibitory concentrations significantly reduced biofilm formation across most tested strains, with inhibition rates varying from 21% to 90.43%. The effectiveness of biofilm inhibition was dependent on the bacterial strain, olive tree variety, and extract concentration used. Statistical analysis confirmed the significance of these results (p < 0.05). Given the demonstrated antioxidant, antibacterial, and antibiofilm properties of these olive tree twig extracts, they show promise for further development as surface disinfectants and potential applications in food safety and infection control. Additional research is warranted to fully characterize their mechanisms of action and optimize their practical applications. Full article
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16 pages, 1563 KiB  
Article
Enhancing Antibiotic Efficacy and Combating Biofilm Formation: Evaluating the Synergistic Potential of Origanum vulgare Essential Oil against Multidrug-Resistant Gram-Negative Bacteria
by Bilal Saoudi, Karim Bariz, Sarah Saci, Yousra Belounis, Hakima Ait Issad, Mohamed Abbaci, Mohamed Abou Mustapha, El-Hafid Nabti, Rawaf Alenazy, Mohammed Sanad Alhussaini, Abdulrahman A. I. Alyahya, Mohammed Alqasmi, Maryam S. Alhumaidi, Fawaz M. Almufarriji and Karim Houali
Microorganisms 2024, 12(8), 1651; https://doi.org/10.3390/microorganisms12081651 - 12 Aug 2024
Cited by 6 | Viewed by 3166
Abstract
Multidrug-resistant (MDR) Gram-negative bacteria remain a global public health issue due to the barrier imposed by their outer membrane and their propensity to form biofilms. It is becoming imperative to develop new antibacterial strategies. In this context, this study aims to evaluate the [...] Read more.
Multidrug-resistant (MDR) Gram-negative bacteria remain a global public health issue due to the barrier imposed by their outer membrane and their propensity to form biofilms. It is becoming imperative to develop new antibacterial strategies. In this context, this study aims to evaluate the antibacterial efficacy of Origanum vulgare essential oil (OEO), alone and in combination with antibiotics, as well as its antibiofilm action against multidrug-resistant Gram-negative strains. OEO components were identified by gas chromatography-mass spectrometry (GC-MS), and antibacterial activity was assessed using the agar diffusion test and the microdilution method. Interactions between OEO and antibiotics were examined using the checkerboard method, while antibiofilm activity was analyzed using the crystal violet assay. Chemical analysis revealed that carvacrol was the major compound in OEO (61.51%). This essential oil demonstrated activity against all the tested strains, with inhibition zone diameters (IZDs) reaching 32.3 ± 1.5 mm. The combination of OEO with different antibiotics produced synergistic and additive effects, leading to a reduction of up to 98.44% in minimum inhibitory concentrations (MICs). In addition, this essential oil demonstrated an ability to inhibit and even eradicate biofilm formation. These results suggest that OEO could be exploited in the development of new molecules, combining its metabolites with antibiotics. Full article
(This article belongs to the Special Issue Healthcare-Associated Infections and Antimicrobial Therapy)
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13 pages, 3133 KiB  
Article
Identification of Potential Therapeutics of Mentha Essential Oil Content as Antibacterial MDR Agents against AcrAB-TolC Multidrug Efflux Pump from Escherichia coli: An In Silico Exploration
by Rawaf Alenazy
Life 2024, 14(5), 610; https://doi.org/10.3390/life14050610 - 9 May 2024
Cited by 2 | Viewed by 1637
Abstract
Multidrug-resistant bacterial pathogens, such as E. coli, represent a major human health threat. Due to the critical need to overcome this dilemma, since the drug efflux pump has a vital function in the evolution of antimicrobial resistance in bacteria, we have investigated [...] Read more.
Multidrug-resistant bacterial pathogens, such as E. coli, represent a major human health threat. Due to the critical need to overcome this dilemma, since the drug efflux pump has a vital function in the evolution of antimicrobial resistance in bacteria, we have investigated the potential of Mentha essential oil major constituents (119) as antimicrobial agents via their ability to inhibit pathogenic DNA gyrase and, in addition, their potential inhibition of the E. coli AcrB-TolC efflux pump, a potential target to inhibit MDR pathogens. The ligand docking approach was conducted to analyze the binding interactions of Mentha EO constituents with the target receptors. The obtained results proved their antimicrobial activity through the inhibition of DNA gyrase (1kzn) with binding affinity ΔG values between −4.94 and −6.49 kcal/mol. Moreover, Mentha EO constituents demonstrated their activity against MDR E. coli by their ability to inhibit AcrB-TolC (4dx7) with ΔG values ranging between −4.69 and −6.39 kcal/mol. The antimicrobial and MDR activity of Mentha EOs was supported via hydrogen bonding and hydrophobic interactions with the key amino acid residues at the binding site of the active pocket of the targeted receptors. Full article
(This article belongs to the Topic Plant Extracts and Their Therapeutic Effects)
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16 pages, 11060 KiB  
Article
Antibacterial Properties of Methanolic Leaf Extracts of Melia azedarach L. against Gram-Positive and Gram-Negative Pathogenic Bacteria
by Soraya Naila Touzout, Abderrahmen Merghni, Aicha Laouani, Halima Boukhibar, Rawaf Alenazy, Abdulmohsen Alobaid, Mustafa Alenazy, Mossadok Ben-Attia, Khaled Saguem and Safia El-Bok
Microorganisms 2023, 11(8), 2062; https://doi.org/10.3390/microorganisms11082062 - 11 Aug 2023
Cited by 5 | Viewed by 3198
Abstract
Melia azedarach L., a Meliaceae family tree, is widely used in traditional folkloric medicine for its pharmaceutical properties. In the present study, we investigated the phytochemical composition of four methanolic leaf extracts of M. azedarach of various origins (Algeria and Tunisia) using high-performance [...] Read more.
Melia azedarach L., a Meliaceae family tree, is widely used in traditional folkloric medicine for its pharmaceutical properties. In the present study, we investigated the phytochemical composition of four methanolic leaf extracts of M. azedarach of various origins (Algeria and Tunisia) using high-performance liquid chromatography (HPLC). The antibacterial efficacy and mechanisms of action against Gram-positive and Gram-negative pathogenic microorganisms were then evaluated. Our findings revealed a presence of phenolic acids and flavonoids, such as gallic acid, chlorogenic acid, caffeic acid, hyperoside, isoquercetin, quercetin, and isorhamnetin both in Algerian and Tunisian localities, with an abundance of phenolic acids compared to flavonoids. Additionally, the studied extracts exhibit a broad spectrum of antibacterial activities, with MIC values ranging from 31.25 mg/mL to 125 mg/mL. Methanolic leaf extracts of M. azedarach from Algeria exhibited more potent biofilm eradication, with a percentage of inhibition reaching 72.17% against the S. aureus strain. Furthermore, inhibitory concentrations of tested substances, particularly the extract from the Relizane area, were capable of disrupting the membrane integrity of the treated bacteria as well as producing oxidative stress through ROS generation. Likewise, our results reveal that plant extract induces lipid peroxidation by raising MDA levels in comparison to untreated cells, particularly with the plant extract of Blida. M. azedarach extracts also reduced the synthesis of antioxidant enzymes (CAT and SOD). Our findings illustrate that M. azedarach remains a plant with significant antibacterial potential and distinct mechanisms of action that are closely related to the origins of this specimen. Full article
(This article belongs to the Special Issue Mechanisms of Antimicrobial Resistance in Bacterial Pathogens)
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16 pages, 2129 KiB  
Article
Chemical Composition of Ailanthus altissima (Mill.) Swingle Methanolic Leaf Extracts and Assessment of Their Antibacterial Activity through Oxidative Stress Induction
by Halima Boukhibar, Aicha Laouani, Soraya Naila Touzout, Rawaf Alenazy, Mohammed Alqasmi, Yaseen Bokhari, khaled Saguem, Mossadok Ben-Attia, Safia El-Bok and Abderrahmen Merghni
Antibiotics 2023, 12(8), 1253; https://doi.org/10.3390/antibiotics12081253 - 29 Jul 2023
Cited by 5 | Viewed by 2844
Abstract
The present study was conducted to investigate the chemical composition of Ailanthus altissima (Mill.) Swingle methanolic leaf extracts from geographically distinct regions and to assess their antimicrobial properties along with their ability to induce oxidative stress. The HPLC-DAD analysis revealed the presence of [...] Read more.
The present study was conducted to investigate the chemical composition of Ailanthus altissima (Mill.) Swingle methanolic leaf extracts from geographically distinct regions and to assess their antimicrobial properties along with their ability to induce oxidative stress. The HPLC-DAD analysis revealed the presence of phenolic acids and flavonoids including chlorogenic acid, gallic acid, synapic acid, p-coumaric acid, apigenin, hyperoside, isoamnétine-3-O-beta-D-glucotrioside, quercetin, and isoquercetin in various amounts depending on the origin of tested extracts. The assessment of antibacterial activity showed the effectiveness of the A. altissima extracts particularly against Gram-positive bacteria, with inhibition zone diameters reaching 14 ± 1 mm and minimum inhibitory concentrations ranging from 4 to 72.2 mg/mL. These bioactive substances also exhibited strong antibiofilm activity with an eradication percentage reaching 67.07%. Furthermore, they increased ROS production to levels two to five times higher than the control group, altered the membrane integrity and caused lipid peroxidation with MDA production exceeding 2.5 µmol/mg protein in the Gram-positive and Gram-negative strains. A decrease in the levels of the antioxidant enzymes SOD and CAT was also observed, indicating an impairment of the bacterial response to the oxidative stress caused by the tested extracts. These findings highlight the antibacterial properties of A. altissima leaf extracts depending on their origins and promote their exploitation and application in the agro-food and pharmaceutical sectors. Full article
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13 pages, 306 KiB  
Article
Comparative Bioactivity Evaluation of Chemically Characterized Essential Oils Obtained from Different Aerial Parts of Eucalyptus gunnii Hook. f. (Myrtaceae)
by Hocine Abbaci, El-hafid Nabti, Abdullah M. Al-Bekairi, Soheir A. A. Hagras, Mounir M. Salem-Bekhit, Abdenour Adjaoud, Hayat Ali Alzahrani, Leila Bensidhoum, Rawaf Alenazy, Alessandra Piras, Danilo Falconieri, Silvia Porcedda, Yacine Benguerba and Karim Houali
Molecules 2023, 28(6), 2638; https://doi.org/10.3390/molecules28062638 - 14 Mar 2023
Cited by 2 | Viewed by 2334
Abstract
Essential oils (EOs) obtained by hydro-distillation from different parts of twigs (EOT), leaves (EOL), and fruits (EOF) of Eucalyptus gunnii Hook. f. were screened for their chemical composition, insecticidal, repellence, and antibacterial properties. Based on GC and GC/MS analysis, 23 constituents were identified [...] Read more.
Essential oils (EOs) obtained by hydro-distillation from different parts of twigs (EOT), leaves (EOL), and fruits (EOF) of Eucalyptus gunnii Hook. f. were screened for their chemical composition, insecticidal, repellence, and antibacterial properties. Based on GC and GC/MS analysis, 23 constituents were identified across the twigs, leaves, and fruits, with 23, 23, and 21 components, respectively. The primary significant class was oxygenated monoterpenes (82.2–95.5%). The main components were 1,8-cineole (65.6–86.1%), α-terpinyl acetate (2.5–7.6%), o-cymene (3.3–7.5%), and α-terpineol (3.3–3.5%). All three EOs exhibited moderate antibacterial activities. EOL was found to have higher antibacterial activity against all tested strains except Dickeya solani (CFBP 8199), for which EOT showed more potency. Globally, Dickeya solani (CFBP 8199) was the most sensitive (MIC ≤ 2 mg/mL), while the most resistant bacteria were Dickeya dadantii (CFBP 3855) and Pectobacterium carotovorum subsp. carotovorum (CFBP 5387). Fumigant, contact toxicity, and repellent bioassays showed different potential depending on plant extracts, particularly EOT and EOL as moderate repellents and EOT as a medium toxicant. Full article
(This article belongs to the Special Issue Biological Activity of Phenolics and Polyphenols in Nature Products)
12 pages, 3797 KiB  
Article
Antimicrobial Activities and Biofilm Inhibition Properties of Trigonella foenumgraecum Methanol Extracts against Multidrug-Resistant Staphylococcus aureus and Escherichia coli
by Rawaf Alenazy
Life 2023, 13(3), 703; https://doi.org/10.3390/life13030703 - 5 Mar 2023
Cited by 9 | Viewed by 4911
Abstract
Multidrug-resistant bacteria are becoming the leading cause of death globally due to their resistance to many currently used antibiotics. Bacteria naturally have intrinsic resistance or acquired resistance to certain commonly used antibiotics. Therefore, searching for novel compounds has become necessary. Trigonella foenumgraecum extract [...] Read more.
Multidrug-resistant bacteria are becoming the leading cause of death globally due to their resistance to many currently used antibiotics. Bacteria naturally have intrinsic resistance or acquired resistance to certain commonly used antibiotics. Therefore, searching for novel compounds has become necessary. Trigonella foenumgraecum extract was evaluated for antimicrobial and antibiofilm activities against multidrug-resistant bacteria Staphylococcus aureus and Escherichia coli. The minimum inhibitory concentration and minimum bactericidal concentration of the extract were also determined. Moreover, gas chromatography-mass spectrometry (GC-MS) analysis was used to identify the phytochemical components present in the extract. GC-MS analysis revealed that T. foenumgraecum extract contains major compounds such as Phenol, 2-methoxy-3-(2-propenyl)-, n-Hexadecanoic acid, and 9,12,15-Octadecatrienoic acid. Both bacterial strains showed resistance to some of the antibiotics tested. T. foenumgraecum showed inhibitory activity against the tested bacterial strains with a MIC of 500 µg/mL and MBC of 1000 µg/mL. The methanol extract decreased the biofilm activity of both E. coli and S. aureus below the sub-minimum inhibitory concentration. The extract showed antibacterial and antibiofilm activity against the tested bacterial pathogens. Full article
(This article belongs to the Collection Antimicrobial Resistance)
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18 pages, 282 KiB  
Article
A First Report on Side-Effects of COVID-19 Vaccines among General Population in Sudan: A Cross-Sectional Analysis
by Malik Suliman Mohamed, Ahmed Osman Mohamed, Rawaf Alenazy, Yusra Habib Khan, Mona Timan Idriss, Noura A. A. Alhudaib, Tilal Elsaman, Magdi Awadalla Mohamed, Eyman M. Eltayib and Tauqeer Hussain Mallhi
Vaccines 2023, 11(2), 315; https://doi.org/10.3390/vaccines11020315 - 31 Jan 2023
Cited by 8 | Viewed by 2925
Abstract
Background: The process of mass immunization against COVID-19 may be impacted by vaccine reluctance despite intense and ongoing efforts to boost vaccine coverage. The COVID-19 vaccine is a crucial component for controlling the pandemic. To the best of our knowledge, we did not [...] Read more.
Background: The process of mass immunization against COVID-19 may be impacted by vaccine reluctance despite intense and ongoing efforts to boost vaccine coverage. The COVID-19 vaccine is a crucial component for controlling the pandemic. To the best of our knowledge, we did not come across any study presenting the post-vaccination side-effect profile among the Sudanese population. Developing strategies to improve the vaccine acceptability and uptake necessitate evidence-based reports about vaccine’s side effects and acceptance. In this regard, this study aimed at estimating the prevalence of COVID-19 vaccine side-effects among the general population in Sudan. Methodology: A cross-sectional web-based quantitative study was conducted among the general population aged ≥18 years and residing in the Khartoum state of Sudan. A 30-item survey tool recorded the demographics, chronic diseases, allergy to other vaccines and COVID-19 vaccine side-effects after the first, second and booster doses. The data on the onset and duration of side-effects after each dose were also recorded. The distribution of side-effect scores after each dose of COVID-19 vaccine was compared using appropriate statistical methods. Results: A total of 626 participants were approached for this study. There was a preponderance of females (57.7%), and 19% of respondents had chronic diseases. The vaccination rate against COVID-19 was 55.8% (n = 349/626). The prevalence of side-effects after the first, second and booster doses were 79.7, 48 and 69.4%, respectively. Pain at the injection site, headache, fatigue, exhaustion and fever were the common side-effects after the first and second doses, while pain at the injection site, fatigue, headache and muscle pain were frequently reported after the booster dose. Most of these side-effects appeared within 6 h and resolved within one or two days following the administration of the vaccine dose. The average side-effects scores were 4.1 ± 4.4 (n = 349), 2.2 ± 3.6 (n = 202) and 3.5 ± 4.1 (n = 36) after the first, second and booster doses, respectively. The female gender had significantly higher side-effects after primary and booster doses. The age group 18-24 years indicated higher side-effects after the first dose compared to participants with ages ranging from 31 to 40 years (p = 0.014). Patients with chronic disease indicated significantly higher (p = 0.043) side-effects compared to those without any comorbid illness. Conclusions: This study showed a high prevalence of transient COVID-19 vaccine-related side-effects after primary and booster doses. However, these side-effects waned within 48 h. Pain at the injection site was the most common local side-effect, while fatigue, fever, headache and muscle pain were frequently reported systemic side-effects. The frequency of side-effects was more profound among females, young adults and those with comorbid conditions. These findings indicate that COVID-19 vaccines are safe and have side-effects as reported in the clinical trials of the vaccines. These results aid in addressing the ongoing challenges of vaccine hesitancy in the Sudanese population that is nurtured by widespread concerns over the safety profile. Full article
(This article belongs to the Special Issue Allergic Reactions to Current Available COVID-19 Vaccines)
20 pages, 3188 KiB  
Review
Drug Efflux Pump Inhibitors: A Promising Approach to Counter Multidrug Resistance in Gram-Negative Pathogens by Targeting AcrB Protein from AcrAB-TolC Multidrug Efflux Pump from Escherichia coli
by Rawaf Alenazy
Biology 2022, 11(9), 1328; https://doi.org/10.3390/biology11091328 - 8 Sep 2022
Cited by 52 | Viewed by 14100
Abstract
Infections caused by multidrug resistance (MDR) of Gram-negative bacteria have become one of the most severe public health problems worldwide. The main mechanism that confers MDR to bacteria is drug efflux pumps, as they expel a wide range of compounds, especially antibiotics. Among [...] Read more.
Infections caused by multidrug resistance (MDR) of Gram-negative bacteria have become one of the most severe public health problems worldwide. The main mechanism that confers MDR to bacteria is drug efflux pumps, as they expel a wide range of compounds, especially antibiotics. Among the different types of drug efflux pumps, the resistance nodulation division (RND) superfamily confers MDR to various Gram-negative bacteria species. The AcrAB-TolC multidrug efflux pump, from E. coli, a member of RND, is the best-characterized example and an excellent model for understanding MDR because of an abundance of functional and structural data. Small molecule inhibitors that target the AcrAB-TolC drug efflux pump represent a new solution to reversing MDR in Gram-negative bacteria and restoring the efficacy of various used drugs that are clinically relevant to these pathogens, especially in the high shortage of drugs for multidrug-resistant Gram-negative bacteria. This review will investigate solutions of MDR in Gram-negative bacteria by studying the inhibition of the AcrAB-TolC multidrug efflux pump. Full article
(This article belongs to the Special Issue Antibiotic Resistance: Linking Phenotypes and Mechanisms)
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17 pages, 3899 KiB  
Article
Formulation of Self-Nanoemulsifying Drug Delivery System of Cephalexin: Physiochemical Characterization and Antibacterial Evaluation
by Ameeduzzafar Zafar, Mohd Yasir, Nabil K. Alruwaili, Syed Sarim Imam, Omar Awad Alsaidan, Sultan Alshehri, Mohammed M. Ghoneim, Ali Alquraini, Alenazy Rawaf, Mohammad Javed Ansari and Udai Vir Singh Sara
Polymers 2022, 14(5), 1055; https://doi.org/10.3390/polym14051055 - 7 Mar 2022
Cited by 26 | Viewed by 3749
Abstract
A cephalexin (CEP) self-nanoemulsifying drug delivery system (SNEDDS) was developed in this study to improve the drug’s oral administration. The CEP-SNEDDS was made utilizing an aqueous titration method employing Lauroglycol 90, Poloxamer 188, and Transcutol-HP. Box-Behnken design (BBD) with three factors at three [...] Read more.
A cephalexin (CEP) self-nanoemulsifying drug delivery system (SNEDDS) was developed in this study to improve the drug’s oral administration. The CEP-SNEDDS was made utilizing an aqueous titration method employing Lauroglycol 90, Poloxamer 188, and Transcutol-HP. Box-Behnken design (BBD) with three factors at three levels was used for optimization, and their impacts on globule size (nm), transmittance (percent), and emulsification time (s) were assessed. The optimized formulation (Opt-F3) was further tested for zeta potential, refractive index, percent transmittance, thermodynamic stability, in-vitro release, ex vivo permeability, antibacterial activity, and bioavailability. The chosen formulation (Opt-F3) had a globule size of 87.25 ± 3.16 nm, PDI of 0.25, zeta potential of −24.37 mV, self-emulsification duration of 52 ± 1.7 s, and percentage transmittance of 99.13 ± 1.5%, viscosity of 96.26 ± 2.72 cp, and refractive index of 1.29 ± 0.1. It showed a sustained release profile (94.28 ± 5.92 percent in 24 h). The Opt-F3 formulation had 3.95 times the permeability of CEP-dispersion. In comparison to CEP-dispersion, it also demonstrated greater antibacterial efficacy against tested Gram-positive and Gram-negative pathogens. The oral bioavailability of Opt-F3 is 3.48 times higher than that of CEP-dispersion, according to an in-vivo investigation. It has been determined that the prepared CEP-SNEDDS may be an advantageous carrier for CEP delivery. Full article
(This article belongs to the Special Issue Novel Polymers and Nanocomposites)
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16 pages, 4658 KiB  
Article
Development and Optimization of Nanolipid-Based Formulation of Diclofenac Sodium: In Vitro Characterization and Preclinical Evaluation
by Ameeduzzafar Zafar, Nabil K Alruwaili, Syed Sarim Imam, Mohd Yasir, Omar Awad Alsaidan, Ali Alquraini, Alenazy Rawaf, Bader Alsuwayt, Md. Khalid Anwer, Sultan Alshehri and Mohammed M. Ghoneim
Pharmaceutics 2022, 14(3), 507; https://doi.org/10.3390/pharmaceutics14030507 - 25 Feb 2022
Cited by 19 | Viewed by 3052
Abstract
In the present research study, we formulate bilosomes (BMs) of diclofenac (DC) for oral delivery for enhancement of therapeutic efficacy (anti-inflammatory disease). The BMS were prepared by thin film hydration method and optimized by Box–Behnken design (BBD) using cholesterol (A), lipid (B), surfactant [...] Read more.
In the present research study, we formulate bilosomes (BMs) of diclofenac (DC) for oral delivery for enhancement of therapeutic efficacy (anti-inflammatory disease). The BMS were prepared by thin film hydration method and optimized by Box–Behnken design (BBD) using cholesterol (A), lipid (B), surfactant (C), and bile salt (D) as formulation factors. Their effects were evaluated on vesicle size (Y1) and entrapment efficacy (Y2). The optimized DC-BMs-opt showed a vesicle size of 270.21 ± 3.76 nm, PDI of 0.265 ± 0.03, and entrapment efficiency of 79.01 ± 2.54%. DSC study result revealed that DC-BMs-opt exhibited complete entrapment of DC in BM matrix. It also depicted significant enhancement (p < 0.05) in release (91.82 ± 4.65%) as compared to pure DC (36.32 ± 4.23%) and DC-liposomes (74.54 ± 4.76%). A higher apparent permeability coefficient (2.08 × 10−3 cm/s) was also achieved compared to pure DC (6.6 × 10−4 cm/s) and DC-liposomes (1.33 × 10−3 cm/s). A 5.21-fold and 1.43-fold enhancement in relative bioavailability was found relative to pure DC and DC liposomes (DC-LP). The anti-inflammatory activity result showed a significant (p < 0.05) reduction of paw edema swelling compared to pure DC and DC-LP. Our findings revealed that encapsulation of DC in BMs matrix is a good alternative for improvement of therapeutic efficacy. Full article
(This article belongs to the Special Issue Novel Approaches for Overcoming Biological Barriers)
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17 pages, 4064 KiB  
Article
Formulation of Genistein-HP β Cyclodextrin-Poloxamer 188 Ternary Inclusion Complex: Solubility to Cytotoxicity Assessment
by Ameeduzzafar Zafar, Nabil K. Alruwaili, Syed Sarim Imam, Omar Awad Alsaidan, Faisal K. Alkholifi, Khalid Saad Alharbi, Ehab M. Mostafa, Abdullah S. Alanazi, Sadaf Jamal Gilani, Arafa Musa, Sultan Alshehri, Alenazy Rawaf and Ali Alquraini
Pharmaceutics 2021, 13(12), 1997; https://doi.org/10.3390/pharmaceutics13121997 - 24 Nov 2021
Cited by 28 | Viewed by 3062
Abstract
The current study was designed to prepare the inclusion complex Genistein (GS) using Hydroxypropyl β cyclodextrin (HP β CD) and poloxamer 188 (PL 188). The binary inclusion complex (GS BC) and ternary inclusion complex (GS TC) were developed by microwave irradiation technique and [...] Read more.
The current study was designed to prepare the inclusion complex Genistein (GS) using Hydroxypropyl β cyclodextrin (HP β CD) and poloxamer 188 (PL 188). The binary inclusion complex (GS BC) and ternary inclusion complex (GS TC) were developed by microwave irradiation technique and evaluated for a comparative dissolution study. Further, the samples were assessed for FTIR, DSC, XRD, and NMR for the confirmation of complex formation. Finally, antioxidant and antimicrobial studies and cytotoxicity studies on a breast cancer (MCF-7) cell line were conducted. The dissolution study result showed a marked increment in GS dissolution/release after incorporation in binary (GS: HP β CD, 1:1) and ternary (GS: HP β CD: PL 188; 1:1:0.5) inclusion complexes. Moreover, the ternary complex exhibited a significant enhancement (p < 0.05) in dissolution than did the binary complexes. This might be due to the presence of PL 188, which helps in solubility enhancement of GS. DSC, XRD and SEM evaluation confirmed the modification in the structure of GS. FTIR and NMR results indicated the formation of an inclusion complex. The antioxidant and antimicrobial activity results revealed that GS TC has shown significant (p < 0.05) higher activity than pure GS. The cytotoxicity study results also depicted concentration-dependent cytotoxicity. GS TC exhibited significantly (p < 0.05) high cytotoxicity to cancer cells (IC50 = 225 µg/mL) than pure GS (IC50 = 480 µg/mL). Finally, it was concluded that a remarkable enhancement in the dissolution was observed after the inclusion of GS in the ternary complex and it therefore has significant potential for the treatment of breast cancer. Full article
(This article belongs to the Special Issue Novel Cyclodextrin Based Systems for Drug Delivery and Related Issues)
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