Effect of C7-3-Peptide-Loaded Chitosan Nanoparticles Against Multi-Drug-Resistant Neisseria gonorrhoeae.

Introduction: The emergence of Neisseria gonorrhoeae-resistant strains represents one of the most urgent global threats. In this regard, C7-3 peptide is one of the anti-virulence therapies that has demonstrated promising anti-gonococcal activity. Accordingly, this research aimed to formulate C7-3 peptide and its derivatives in chitosan nanoparticles. Methods: The peptide loaded chitosan nanoparticles were prepared using ion gelation method, and their physicochemical characteristics were investigated. The anti-gonococcal and antibiofilm activity of prepared NPs was assessed, and their cytotoxicity in human ovarian cells was evaluated. Results: All prepared NPs were optimized for the smallest particle size of 136.9 to 168.3 nm. The EE% of C7-3, C7-3m1, and C7-3m2 CNPs reached 90.2, 92.5, and 91.8%, respectively. An in vitro release study demonstrated a continuous sustained-release pattern of C7-3 peptide from NPs. The SDS-PAGE assay confirmed the integrity of C7-3 peptide after the fabrication process. When comparing each peptide alone, the generated NPs demonstrated higher anti-gonococcal and anti-biofilm effectiveness against standard and resistant bacterial strains under anaerobic conditions. The cytotoxicity experiments revealed the cytocompatibility of NPs in HeLa cell lines. Given the advantages of enhanced anti-gonococcal activity of the C7-3 peptide and its derivatives when loaded with CNPs, as well as the antimicrobial properties of chitosan NPs, the reported NPs have great potential in the treatment of gonococcal infection.

Evaluation of the Clinical Outcome and Cost Analysis of Antibiotics in the Treatment of Acute Respiratory Tract Infections in the Emergency Department in Saudi Arabia.

This study aims to assess the prevalence and antibiotic-treatment patterns of respiratory tract infections (RTIs), prevalence and types of antibiotic-prescribing errors, and the cost of inappropriate antibiotic use among emergency department (ED) patients. A cross-sectional study was conducted at the ED in King Abdulaziz Medical City, Riyadh, Saudi Arabia. Patient characteristics (age, sex, weight, allergies, diagnostic tests (CX-Ray), cultures, microorganism types, and prescription characteristics) were studied. During the study, 3185 cases were diagnosed with RTIs: adults (>15 years) 55% and pediatrics (<15 years) 44%. The overall prevalence of RTIs was 21%, differentiated by upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) (URTI 13.4%; LRTI 8.4%), of total visits. Three main antibiotics (ATB) categories were prescribed in both age groups: penicillin (pediatrics 43%; adults 26%), cephalosporin (pediatrics 29%; adults 19%), and macrolide (pediatrics 26%; adults 38%). The prevalence of inappropriate ATB prescriptions was 53% (pediatrics 35%; adults 67%). Errors in ATB included selection (3.3%), dosage (22%), frequency (3%), and duration (32%). There is a compelling need to create antimicrobial stewardship (AMS) programs to improve antibiotic use due to the high number of prescriptions in the ED deemed as inappropriate. This will help to prevent unwanted consequences on the patients and the community associated with antibiotic use.

Attenuation of Pseudomonas aeruginosa Quorum Sensing Virulence of Biofilm and Pyocyanin by mBTL-Loaded Calcium Alginate Nanoparticles.

Pseudomonas aeruginosa contributes to many chronic infections and has been found to be resistant to multiple antibiotics. Pseudomonas use a quorum sensing system (QS) to control biofilm establishment and virulence factors, and, thus, quorum sensing inhibitors (QSIs), such as meta-bromo-thiolactone (mBTL), are promising anti-infective agents. Accordingly, this study intended to investigate the antibacterial and anti-virulence activity of mBTL-loaded calcium alginate nanoparticles (CANPs) against Pseudomonas aeruginosa and different QS mutants. The results show that the mBTL-CANPs had higher antibacterial activity, which was made evident by decreases in all tested strains except the ∆lasR/∆rhlR double mutant, with MIC50 (0.5 mg/mL) of mBTL-CANPs compared with free mBTL at MIC50 (˃1 mg/mL). The biofilm formation of P. aeruginosa and some QS-deficient mutants were reduced in response to 0.5-0.125 mg/mL of mBTL-encapsulating CANPs. The pyocyanin production of the tested strains except ∆lasA and ∆rhlR decreased when challenged with 0.5 mg/mL of mBTL-loaded NPs. The subsequent characterization of the cytotoxic effect of these NPs on human lung epithelial cells (A549) and cystic fibrosis fibroblast cells (LL 29) demonstrated that synthesized NPs were cytocompatible at MIC50 in both cell lines and markedly reduced the cytotoxic effect observed with mBTL alone on these cells. The resulting formulation reduced the P. aeruginosa strains' adhesion to A549 comparably with mBTL, suggesting their potential anti-adhesive effect. Given the virulence suppressing action, cytocompatibility, and enhanced anti-biofilm effect of mBTL-CANPs, and the advantage of alginate-based NPs as an antimicrobial delivery system these nanoparticles have great potential in the prophylaxis and treatment of infection caused by Pseudomonas aeruginosa.

Risk management and infection control preparedness of Saudi healthcare facilities to overcome the COVID-19 pandemic.

Objective: To evaluate the preparedness of Saudi healthcare facilities to handle the coronavirus disease 2019 (COVID-19) pandemic. Methods: Between April and June 2020, a cross-sectional study was conducted among Saudi hospitals using an online-administered English-language questionnaire by the Saudi Commission for Health Specialties. The questionnaire evaluates all aspects of risk management, infection control and preventative programmes that should be known and practised by all healthcare workers (HCWs). All HCWs in Saudi hospitals designated to accept patients with COVID-19 were involved in the study. Results: In total, 161 HCWs responded to the survey. General understanding of hospital risk management plans and infection prevention measures was found to be outstanding (80.4%), with no differences in responses by gender, education or occupation. Some differences in responses were found by age group and years of working experience. Most responses were from hospitals located in the Central Province (72.7%) and governmental hospitals (88%), and most provided family services (68%). Furthermore, the results showed that medical professionals received adequate training, which is recognized as the baseline for effective risk management and infection control and prevention procedures, policies and recommendations. Conclusions: Notwithstanding small differences between HCWs, this study found that all HCWs in Saudi hospitals had excellent knowledge of risk management plans and pandemic sub-plans of infection control and prevention policies, procedures and principles, which has aided the health authorities in Saudi Arabia in mitigating COVID-19 effectively.

MicroRNA-219 loaded chitosan nanoparticles for treatment of glioblastoma.

Recent evidence has implicated microRNA-219 (miR-219) in regulation of gene contributed in glioblastoma (GBM) pathogenesis. This study aimed to prepare miR-219 in chitosan (CS) nanoparticles (NPs), characterize and investigate their efficacy on human GBM cell line (U87 MG). NPs were prepared using ionic gelation method. The influence of process parameters on physicochemical characteristics of NPs was investigated. Apoptotic effect of miR-219 was examined on U87 MG cells. Formulated NPs showed particle size of 109 ± 2.18 nm, with poly dispersity index equal to 0.2 ± 0.05, and zeta potential of +20.5 ± 0.7 mV. Entrapment efficiency of miR-219 in loaded NP has reached 95%. The in vitro release study demonstrated sustained release pattern of miR-219 from CS-NPs. Gel retardation assay has confirmed the integrity of miR-219 after production process. The fabricated NPs reduced the survival of U87 MG cells to 78% after 24 h of post-transfection, and into 67.5% after 48 h. However, fibroblasts were not affected by the NPs, revealing their specificity for GBM cells. Given the tumour suppressing function of miR-219, and advantage of CS-NPs for gene delivery to the central nervous system, the presented NPs have a great potential for treatment of GBM.

Association Between Obesity and COVID-19 Disease Severity in Saudi Population.

Background: The persistent coronavirus disease 2019 (COVID-19) outbreak has placed a significant burden on the scientific and medical professions. The study examined the association between body mass index (BMI), stratified by category, and severe form of COVID-19, and to explore the influence of demographic characteristics and other known risk factors. Methods: This was a retrospective analysis based on COVID-19 data from the Saudi Arabian Ministry of Health. Data were collected for all patients admitted to three main hospitals in Riyadh region between March 1st and July 30, 2020. The effects of BMI, demographic characteristics, clinical presentation, and comorbidities on infection severity were investigated. Results: A total of 950 patients were included in the study (70% male, 85% aged younger than 60 years old). A total of 55 (5.8%) patients were underweight, 263 (27.7%) were normal weight, 351 (37%) were overweight, 161 (17%) were obese class I, 76 (8%) were obese class II, and 44 (4.6%) were obese class III. Cough, fever, and shortness of breath were the most common symptoms among overweight patients. According to the findings of a bivariate logistic regression study, class III obesity was significantly associated with a more severe form of COVID-19 (odds ratio, 2.874; 95% confidence interval, 1.344-6.149). Conclusion: This study revealed that patients with a BMI ≥40 kg/m2 had a higher risk of severe COVID-19 than those with normal weight. This suggests that obesity is a risk factor for severe COVID-19 and influences disease presentation.

MicroRNA-539-5p-Loaded PLGA Nanoparticles Grafted with iRGD as a Targeting Treatment for Choroidal Neovascularization.

Choroidal neovascularization (CNV) is a major cause of visual impairment that results from excessive growth of blood vessels in the eye's choroid. The limited clinical efficacy of the current therapy for this condition requires the emergence of new treatment modalities such as microRNA (miRNAs). A recent study identified microRNA-539-5p (miR-539) as an angiogenic suppressor in a CNV animal model; however, its therapeutic delivery is limited. Therefore, this study aims to formulate miR-539 in targeted nanoparticles (NPs) prepared from polylactic-co-glycolic acid (PLGA). The NPs were decorated with internalizing arginylglycylaspartic (RGD) peptide (iRGD), which specifically targets the alpha-v-beta-3 (αvß3) integrin receptor that is overexpressed in blood vessels of ocular tissue in CNV patients. The 1H NMR spectra results revealed successful conjugation of iRGD peptide into PLGA NPs. The miR-539-PLGA.NPs and miR-539-iRGD-PLGA.NPs were prepared and showed a particle size of 300 ± 3 and 306.40 ± 4 nm, respectively. A reduction in human retinal microvascular endothelial cell (HRMEC) viability was shown 48 and 72 h post transfection with miR-539 incorporated in PLGA NPs and iRGD-PLGA.NPs. iRGD-functionalized PLGA NPs caused further significant reduction in cell viability when compared with plain ones, revealing an enhancement in the NP uptake with iRGD-grafted NPs. The current study showed that miR-539-PLGA.NPs and miR-539-iRGD-PLGA.NPs are promising approaches that reduced the viability of HRMECs, suggesting their therapeutic potential in the treatment of CNV.

Outcomes associated with tocilizumab with or without corticosteroid versus dexamethasone for treatment of patients with severe to critical COVID-19 pneumonia.

INTRODUCTION: Immunomodulators, including dexamethasone (DEX), have been recommended by the Infectious Disease Society of America (IDSA) to treat moderate, severe, and critical COVID-19. Tocilizumab (TCZ) was added to the treatment recommendations based on recent data from two large randomized controlled trials and its potential synergistic effect with DEX. METHOD: We included adult patients admitted from June until October 2020 with a PCR confirmed SARS-CoV-2 infection. 135 patients with severe to critical COVID-19 and received TCZ and/or corticosteroid or DEX were retrospectively evaluated and followed until hospital discharge or death. RESULTS: The cohort was divided into two different groups of patients; TCZ group received TCZ ± corticosteroid, N = 100 and DEX group received DEX, N = 35. Groups were analyzed for hospital mortality. The rate of hospital mortality was 36% in TCZ and 37% in the DEX group, p = 0.91. Age of 60 years and above was associated with higher mortality rate with OR = 1.030 and 95% CI = (1.004, 1.057). More than 50% of patients required MV in both groups. Development of bacterial or fungal infection post immunomodulator were similar in TCZ and DEX groups, 29% vs. 31.4%. CONCLUSION: Our study revealed that age of 60 years and above is the only factor associated with higher mortality rate regardless of the type of immunomodulator therapy. Findings of this study also revealed the lack of synergistic effect between TCZ and DEX on the hospital mortality.

Synthesis, Cytotoxic Evaluation, and Structure-Activity Relationship of Substituted Quinazolinones as Cyclin-Dependent Kinase 9 Inhibitors.

Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcriptional elongation, through which short-lived antiapoptotic proteins are overexpressed and make cancer cells resistant to apoptosis. Therefore, CDK9 inhibition depletes antiapoptotic proteins, which in turn leads to the reinstatement of apoptosis in cancer cells. Twenty-seven compounds were synthesized, and their CDK9 inhibitory and cytotoxic activities were evaluated. Compounds 7, 9, and 25 were the most potent CDK9 inhibitors, with IC50 values of 0.115, 0.131, and 0.142 µM, respectively. The binding modes of these molecules were studied via molecular docking, which shows that they occupy the adenosine triphosphate binding site of CDK9. Of these three molecules, compound 25 shows good drug-like properties, as it does not violate Lipinski's rule of five. In addition, this molecule shows promising ligand and lipophilic efficiency values and is an ideal candidate for further optimization.

Improved delivery of miR-1296 loaded cationic nanoliposomes for effective suppression of triple negative breast cancer.

Nowadays, microRNA is considered an attractive strategy for the effective treatment of cancer. A significant delivery of microRNA for cancer therapy remains a significant obstacle to target cancer cells. The restoring microRNA-1296 (miR-1296) has immense therapeutic efficacy in triple-negative breast cancer (TNBC). TNBC is an aggressive subtype of breast tumors with the progression of malignant transformation. This study aimed to develop a cationic nanoliposome that can serve as a miR-1296 carrier and studied its efficiency in TNBC. The efficacy of miR-1296 liposomes was evaluated on its apoptotic effect, cellular uptake, and potential chemotherapy sensitization in the TNBC cell line (MDA-MB-231). For in vitro viability study, the apoptotic effect was performed to validate protein expression using Alamar blue kit and western blot. The transfection of miR-1296 into TNBC cells was also investigated using cisplatin as a TNBC resistance drug. The fluorescent miR-1296-cy3 liposome was used for cellular uptake study. The miR-liposome was successfully prepared with a particle size of 123.6 ± 1.3 nm and encapsulation efficiency of 94.33%. A dose of 0.5 uM has significantly reduced the viability of MDA-MB-231 to be 33.45%±5.29 (P < 0.001). This result was validated by down-expression of CCND1, and PARP1, the miR-1296 receptor, and apoptosis marker. The image of the miR-1296-cy3 liposome showed cytoplasmic intracellular localization. It was found high sensitization of TNBC cell line for miR-1296 liposome compared to cisplatin (P < 0.001). Future in vivo research may answer questions concerning safety and stability. This study demonstrates that miR-191 liposomes may have promising clinical applications for TNBC therapy.

Awareness and knowledge of COVID-19 infection control precautions and waste management among healthcare workers: Saudi cross-sectional study.

ABSTRACT: Healthcare workers (HWs) perform a critical role not only in the clinical management of patients but also in providing adequate infection control and prevention measures and waste management procedures to be implemented in healthcare facilities. The aim of this study was to evaluate the awareness and knowledge of COVID-19 infection control precautions and waste management procedures among HWs in Saudi Arabian hospitals.This was a descriptive, cross-sectional study. Information on knowledge, awareness, and practice of infection control and waste management procedures were obtained from the HWs using a structured questionnaire. A thematic analysis was used to analyze the data.Our findings indicated that most of the study participants were knowledgeable, with a mean score of 78.3%. In total, 92.5%, 90.3%, and 91.7% of the participants were aware of the infection control precautions, COVID-19 waste management procedures, the availability of infection control supplies, respectively. HWs' Knowledge regarding waste management and infection control procedures correlated significantly with sex (P ≤ .001 and <.001), education (P = .024 and .043), and working experience (P = .029 and .009), respectively.Most participants appreciated the importance of their role in infection control, surveillance, and monitoring of the ongoing safety practices in their patients as well as their facilities and communities.

Impact of Rapid Identification of Staphylococcus Species in Positive Blood Culture Using GeneXpert Methicillin-Resistant Staphylococcus aureus/ Staphylococcus aureus Blood Culture Assay Combined with Antibiotic Stewardship.

Staphylococcus aureus bacteremia is a life-threatening condition associated with a substantial financial burden on the health care system. The use of the GeneXpert® methicillin-resistant S. aureus (MRSA)/S. aureus blood culture (BC) test for the identification of S. aureus may influence antibiotic stewardship and clinical outcomes. This study assessed the clinical and financial impact of utilizing GeneXpert MRSA/SA in combination with criterion-based testing. The outcomes between October 1, 2018, and June 30, 2019, were evaluated in 65 adult patients who had positive BCs with Gram-positive cocci in clusters. GeneXpert MRSA/SA significantly shortened the time to optimal antimicrobial therapy by 1.7 days (2.5 vs. 44 hr, p < 0.0001). The cost saved because of interventions based on GeneXpert testing results was $4,121. GeneXpert testing has shortened the time to optimal therapy and positively impacted cost, although it had no significant effect on length of hospital stay and mortality rate.

Influence of the minimum inhibitory concentration of daptomycin on the outcomes of Staphylococcus aureus bacteraemia.

OBJECTIVES: Recent studies have shown that methicillin-resistantStaphylococcus aureus (MRSA) bacteraemia with vancomycin minimum inhibitory concentration (MIC) >1 µg/mL is associated with a higher rate of treatment failure and a higher mortality rate. Daptomycin is an alternative to vancomycin but has not been as well studied. The aim of this literature review was to evaluate the effect of daptomycin MIC on the outcomes of S. aureus bacteraemia. METHODS: We conducted a literature search for the period January 2010 to January 2019 using the MEDLINE and Embase databases. RESULTS: Four studies were included in the review. The outcomes were clinical cure and 30- or 60-day mortality. In two retrospective studies, 60-70% ofS. aureus isolates had a low daptomycin MIC (≤0.5 µg/mL) and patients with MRSA bacteraemia who were treated with daptomycin had a lower mortality rate. In another study, patients with methicillin-susceptible S. aureus bacteraemia with low daptomycin MICs had a lower risk of developing septic thrombophlebitis. One study showed that patients with MRSA bacteraemia had a higher mortality rate if the daptomycin MIC was >0.5 µg/mL. CONCLUSION: The included studies in this review suggest a possible association between high daptomycin MIC and unfavourable clinical outcomes ofS. aureus bacteraemia. Further prospective studies are required to evaluate the impact of the daptomycin MIC on the clinical outcomes of S. aureus bacteraemia.

Trastuzumab Targeted Neratinib Loaded Poly-Amidoamine Dendrimer Nanocapsules for Breast Cancer Therapy.

BACKGROUND: Human epidermal growth factor receptor2 (Her2) positive breast cancer represents 25% of breast cancer cases. Targeted therapy with Her2 monoclonal antibody, trastuzumab (TZ), represents the first-line treatment for this type of breast cancer. In addition, neratinib, an irreversible inhibitor of the HER-2 receptor tyrosine kinase, has recently been approved as adjuvant therapy to TZ. This study aims to formulate (TZ)-grafted dendrimers loaded with neratinib, allowing a dual treatment alongside reducing the associated resistance as well as targeted therapy. METHODS: TZ was conjugated on the surface of dendrimer using hetero-cross linker, MAL-PEG-NHS, and the zeta potential, and in vitro release of neratinib from dendrimers was characterized. Formulated dendrimers were also fluorescently conjugated with fluorescein isothiocyanate to visualize and quantify their SKBR-3 cellular uptake. RESULTS: The G4 PAMAM dendrimer showed successful encapsulation of neratinib and a sustained release profile. Comparative in vitro studies revealed that these TZ-targeted dendrimers loaded with neratinib were more selective and have higher antiproliferation activity against SKBR-3 cells compared to neratinib alone and neratinib loaded dendrimer. CONCLUSION: In the current study, neratinib loaded in plain and trastuzumab-grafted dendrimer were successfully prepared. Enhanced cellular uptake of trastuzumab conjugated dendrimers was shown, together with a higher cytotoxic effect than plain neratinib dendrimers. These findings suggest the potential of TZ-conjugated dendrimers as targeting carrier for cytotoxic drugs, including neratinib.

Common Co-morbidities Are Challenging in the Diagnosis of Middle East Respiratory Syndrome (MERS-CoV) in Saudi Arabia.

BACKGROUND AND OBJECTIVE: Middle East respiratory syndrome coronavirus (MERS-CoV) is a relatively recent human disease reported initially in Saudi Arabia in September, 2012. Morbidities investigation includes a process of excluding other possible options until certain suspected cases are confirmed. MATERIAL AND METHODS: In this study, we formulated a model under the authorization of the Saudi Ministry of Health to accurately identify cases among admitted suspected cases depending on specific signs and symptoms. Real-time polymerase chain reaction was used for confirmation of the positive cases. RESULTS: The results showed that the number of patients with combined symptoms of fever/sore throat and fever/cough/SOB was significantly higher in confirmed cases than in non-confirmed cases (p<0.05). Besides, the number of confirmed MERS-CoV cases was significantly higher among cases included in the study than excluded cases. It was also clearly demonstrated that fever combined with other symptoms represents 60% of the confirmed cases, which is significantly higher than for cases with other combined symptoms (p<0.0001). CONCLUSION: To the best of our knowledge, there are no appropriate diagnostic models that can differentiate human MERS-CoV infection among other respiratory infections. Therefore, we recommend the adoption of this newly established model of MERS-CoV to short- list corona suspected cases in Saudi Arabia.

Chemical composition and antimicrobial, antioxidant, and anti-inflammatory activities of Lepidium sativum seed oil.

Lepidium sativum (garden cress) seed oil was examined for its antimicrobial, antioxidant, and anti-inflammatory activities. The oil was obtained by hydrodistillation, where gas chromatography coupled with mass spectrometry that utilized to study its chemical composition. Microdilution method was used to test the antimicrobial effect of oil against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Klebsiella pneumoniae, and Candida albicans. The antioxidant activity was assessed by radical scavenging activity assay using 2,2-diphenyl-1-picrylhydrazyl radical. The major constituents found in the oil were 7,10-hexadecadienoic acid, 11-octadecenoic acid, 7,10,13-hexadecatrienoic acid, and behenic acid. The minimum inhibitory concentration (MIC) against all pathogens was 47.5 mg/ml, except for Salmonella enterica, which showed MIC of 90 mg/ml. The oil demonstrated antioxidant activity in a dose dependent pattern, with a half maximal inhibitory concentration (IC50) value of 40 mg/ml, and exerted anti-inflammatory activity, wherein 21% protection was shown at a concentration of 300 µg/ml. Thus, L. sativum seed oil shows antimicrobial, antioxidant, and anti-inflammatory properties.

Synthesis, anticancer, apoptosis-inducing activities and EGFR and VEGFR2 assay mechanistic studies of 5,5-diphenylimidazolidine-2,4-dione derivatives: Molecular docking studies.

A new series of 5,5-diphenylhydantoin derivatives containing benzylidene or isatin (4-19) was synthesized. Their anticancer activity against HeLa, a cervical cancer cell line, A549, a lung cancer cell line, and MDA-MB-231, a breast cancer cell line, was evaluated. Compounds 13, 16, 17 and 18 exhibited potent anticancer activity with average IC50 values against the tested cell lines of 109, 59, 81 and 113 µM, respectively. Compound 16 showed potent EGFR and VEGFR2 inhibitory activity with IC50 values of 6.17 and 0.09 µM, respectively. In addition, compound 16 induced caspase-dependent apoptosis and reactive oxygen species (ROS) production at 5 and 10 µM. Moreover, a molecular docking simulation was performed for compound 16 and sunitinib to predict the protein-ligand interactions with the active site of VEGFR2.

Paclitaxel.

Paclitaxel is the first microtubule-stabilizing agent identified and considered to be the most significant advance in chemotherapy of the past two decades. It is considered one of the most widely used antineoplastic agents with broad activity in several cancers including breast cancer, endometrial cancer, non-small-cell lung cancer, bladder cancer, and cervical carcinoma. It is also used for treating AIDS-related Kaposi sarcoma as a second line treatment. This comprehensive profile of paclitaxel gives overview of nomenclature, formulae, elemental analysis, appearance, application and uses. In addition, mechanism of action and resistance, different dosage forms and methods of drug preparation are elaborated. Moreover, the physicochemical properties involving X-ray powder diffraction pattern, drug solubility, melting point, differential scanning calorimetry, and stability were summarized. Furthermore, method of drug analysis including compendial, spectrophotometric, and chromatographic was discussed.

Preparation, characterization, and antibacterial activity of diclofenac-loaded chitosan nanoparticles.

Emerging antibiotic resistance necessitates the development of new therapeutic approaches. Many studies have reported the antimicrobial activity of diclofenac sodium (DIC) and chitosan nanoparticles (CNPs). Hence, this study aimed to prepare non-antibiotic DIC-loaded CNPs (DIC.CNPs) and characterize their in vitro antibacterial activity. DIC.CNPs were prepared from low and high molecular weight (LMW and HMW, respectively) chitosan using an ionic gelation method. Prepared NPs were characterized, and their antibacterial activity against gram-positive Staphylococcus aureus and Bacillus subtilis was evaluated using the agar diffusion and broth dilution methods. The particle size, polydispersity index (PDI), and encapsulation efficiency of the formulated DIC.CNPs increased with increasing MW of chitosan. The prepared NPs showed a narrow size distribution with low PDI values (0.18 and 0.24) and encapsulation efficiency (29.3% and 31.1%) for LMW.DIC.CNPs and HMW.DIC.CNPs, respectively. The in vitro release profile of DIC from the DIC.CNPs was biphasic with a burst release followed by slow release and was influenced by the MW of chitosan. DIC.CNPs exhibited significantly higher antibacterial activity against S. aureus (minimum inhibitory concentration [MIC90] LMW.DIC.CNPs = 35 µg/mL and MIC90 HMW.DIC.CNPs = 18 µg/mL) and B. subtilis (MIC90 LMW.DIC.CNPs = 17.5 µg/mL and MIC90 HMW.DIC.CNPs = 9 µg/mL) than DIC alone did (MIC90 DIC = 250 and 50 µg/mL against S. aureus and B. subtilis, respectively). The antibacterial activity was influenced by pH and the MW of chitosan. Collectively, these results may suggest the potential usefulness of DIC.CNPs as non-antibiotic antibacterial agent necessitating further future studies to asses the stability of DIC.CNPs prepared.

Exploring anti-MRSA activity of chitosan-coated liposomal dicloxacillin.

One of the greatest disturbing global health problems is antibiotic-resistant bacterial infections, which have rendered numerous currently used antibiotics ineffective. Thus, the feasibility of chitosan-coated deformable liposomes (C-Lips) containing dicloxacillin (DLX) were evaluated for their efficacy against methicillin-resistant Staphylococcus aureus (MRSA) strains, which are resistant to beta lactam antibiotics. DLX-loaded liposomes (DLX-Lip) were prepared by a lipid film hydration method and then chitosan (CS) coated (C-DLX-Lip) by the electrostatic deposition method. Both DLX-Lips and C-DLX-Lips showed a particle size distribution with a nano-range and a narrow polydispersity index (PDI). After CS coating, the zeta potential was shifted from negative to positive value. The DLX entrapment efficiency (EE) and drug loading (DL) were 62% and 5.6% for C-DLX-Lips compared to 38% and 3.1% for DLX-Lip, respectively. The in vitro release profile of C-DLX-Lips possessed a slow release behavior. Moreover, the DLX-Lips and C-DLX-Lips demonstrated an enhanced anti-MRSA activity. These results revealed that DLX-Lips and C-DLX-Lips may serve as promising carriers for DLX to increase the efficacy against MRSA, which offers considerably clinical value for long-term use of DLX.