Isotretinoin self-nano-emulsifying drug delivery system: Preparation, optimization and antibacterial evaluation.

Purpose: Isotretinoin (ITN) is a poorly water-soluble drug. The objective of this study was to design a successful liquid self-nanoemulsifying drug delivery system (L-SNEDDS) for ITN to improve its solubility, dissolution rate, and antibacterial activity. Methods: According to solubility and emulsification studies, castor oil, Cremophor EL, and Transcutol HP were selected as system excipients. A pseudo ternary phase diagram was constructed to reveal the self-emulsification area. The developed SNEDDS were visually assessed, and the droplet size was measured. In vitro release studies and stability studies were conducted. The antimicrobial effectiveness against multiple bacterial strains, including Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and different accessory gene regulator (Agr) variants were investigated for the optimum ITN-loaded SNEDDS formulation. Results: Characterization studies showed emulsion homogeneity and stability (%T 95.40-99.20, A graded) with low droplet sizes (31.87 ± 1.23 nm-115.47 ± 0.36 nm). It was found that the developed ITN-SNEDDS provided significantly a higher release rate (>96 % in 1 h) as compared to the raw drug (<10 % in 1 h). The in vitro antimicrobial activities of pure ITN and ITN-loaded SNEDDS demonstrated a remarkable inhibitory effect on bacterial growth with statistically significant findings (p < 0.0001) for all tested strains when treated with ITN-SNEDDS as compared to the raw drug. Conclusion: These outcomes suggested that SNEDDS could be a potential approach for improving solubility, dissolution rates, and antibacterial activity of ITN.

Anti-quorum sensing activity of poly-amidoamine dendrimer generation 5 dendrimer loaded kinase inhibitor peptide against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant concern in both healthcare and community settings, as it causes numerous infections worldwide with high morbidity and mortality rates. One promising strategy is to target the quorum sensing (QS) system of MRSA using a dendrimer loaded with kinase inhibitor peptide. The present investigation has formulated a poly-amidoamine dendrimer (PAMAM) G5 dendrimer that is loaded with Quorum Quencher (QQ) peptide, which functions as a histidine kinase inhibitor. The particle average size of the formulated G5-QQ3 complex was determined to be 276 nm, and polydispersity index values of 0.33. The MIC50 for the formulated nanoparticles was 18 µM as demonstrated by a growth assay. Furthermore, the G5-QQ3 complex was able to inhibit the hemolysis activity of the MRSA with a concentration of 10 µM, and for Staphylococcus aureus was 3 µM. The G5-QQ3 complex possesses the ability to inhibit, penetrate, and eradicate biofilm in MRSA, Staphylococcus aureus, and different agr mutants with inhibition percentages ranging from 60 to 72%. Furthermore, live/dead viability assay confirmed the ability of the formulated nanoparticles to effectively kill all strains within the biofilm structure as evidenced by a confocal microscope, and the cytotoxicity of the G5-QQ3 complex was dose-dependent (p < 0.05). against RAW 264.7 cells. In general, the study confirmed that encapsulating QQ3 peptide within PAMAM G5 dendrimer results in a potent anti-virulence and anti-bacterial action and suggests a synergistic effect. The findings of this study have significant implications for the development of new treatments for MRSA infections, which are a major public health concern.

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.

Formulation and In Vivo Evaluation of Biofilm Loaded with Silver Sulfadiazine for Burn Healing.

Infected burned skin is a life-threatening condition, which may lead to sepsis. The aims of this work are to formulate a biofilm composed of silver sulfadiazine (SSD), chitosan (CS), and sodium alginate (SA), and to evaluate its wound-healing effectiveness. A full factorial design was used to formulate different matrix formulations. The prepared biofilm was tested for physicochemical, and in vitro release. The optimized formulation is composed of 0.833% of CS and 0.75% of SA. The release of SSD almost reached 100% after 6 h. The mechanical properties of the optimized formula were reasonable. The antibacterial activity for the optimized biofilm was significantly higher than that of blank biofilm, which is composed of CS and SA, p = 1.53922 × 10-12. Moreover, the in vivo study showed a 75% reduction in wound width when using the formulated SSD biofilm compared to standard marketed cream (57%) and the untreated group (0%).

Unlocking the Power of Onion Peel Extracts: Antimicrobial and Anti-Inflammatory Effects Improve Wound Healing through Repressing Notch-1/NLRP3/Caspase-1 Signaling.

Onion peels are often discarded, representing an unlimited amount of food by-products; however, they are a valuable source of bioactive phenolics. Thus, we utilized UPLC-MS/MS to analyze the metabolomic profiles of red (RO) and yellow (YO) onion peel extracts. The cytotoxic (SRB assay), anti-inflammatory (Griess assay), and antimicrobial (sensitivity test, MIC, antibiofilm, and SP-SDS tests) properties were assessed in vitro. Additionally, histological analysis, immunohistochemistry, and ELISA tests were conducted to investigate the healing potential in excisional skin wound injury and Candida albicans infection in vivo. RO extract demonstrated antibacterial activity, limited skin infection with C. albicans, and improved the skin's appearance due to the abundance of quercetin and anthocyanin derivatives. Both extracts reduced lipopolysaccharide-induced nitric oxide release in vitro and showed a negligible cytotoxic effect on MCF-7 and HT29 cells. When extracts were tested in vivo for their ability to promote tissue regeneration, it was found that YO peel extract had the greatest impact. Further biochemical analysis revealed that YO extract suppressed NLRP3/caspase-1 signaling and decreased inflammatory cytokines. Furthermore, YO extract decreased Notch-1 levels and boosted VEGF-mediated angiogenesis. Our findings imply that onion peel extract can effectively treat wounds by reducing microbial infection, reducing inflammation, and promoting tissue regeneration.

Chitosan loaded RNA polymerase inhibitor nanoparticles increased attenuation in toxin release from Streptococcus pneumonia.

Background: Multidrug-resistant (MDR) bacterial infections have become an emerging health concern around the world. Antibiotics resistance among S. pneumoniae strains increased recently contributing to increase in incidence of pneumococcal infection. This necessitates the discovery of novel antipnemococcal such as compound C3-005 which target the interaction between RNA polymerase and σ factors. Chitosan nanoparticles (CNPs) exhibited antibacterial activity including S. pneumonia. Therefore, the aims of the current investigation were to formulate CNPs loaded with C3-005 and characteristic their antimicrobial properties against S. pneumonia. Methods: The CNPs and C3-005 loaded CNPs were produced utilizing ionic gelation method, and their physicochemical characteristics including particle size, zeta potential, polydispersity index (PDI), encapsulation efficiency (EE%), and in vitro release profile were studied. Both differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR) were used for chemical characterization. The synthesized NPs' minimum inhibitory concentration (MIC) was determined using killing assay and broth dilution method, and their impact on bacteria induced hemolysis were also studied. Results: The NPs encapsulating C3-005 were successfully prepared with particle size of 343.5 nm ± 1.3, zeta potential of 29.8 ± 0.37, and PDI of 0.20 ± 0.03. 70 % of C3-005 were encapsulated in CNPs and sustained release pattern of C3-005 from CNPs was revealed by an in vitro release study. CNPs containing C3-005 exhibited higher antipnomcoccal activity with MIC50 of 30 µg/ml when compared with C3-005 and empty CNPs alone. The prepared C3-CNPs showed a reduction of bacterial hemolysis in a concentration-related (dependent) manner and was higher than C3-005 alone. Conclusions: The findings of this study showed the potential for using C3-005 loaded CNPs to treat pneumococcal infection.

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.

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.

Measurement and evaluation of the effects of pH gradients on the antimicrobial and antivirulence activities of chitosan nanoparticles in Pseudomonas aeruginosa.

OBJECTIVE: The purpose of this study was to study the antimicrobial activity of chitosan nanoparticles (CSNPs) on Pseudomonas aeruginosa with special emphasis on their sensitivity to pH and the effect of pH on their activity. METHODOLOGY: Antimicrobial activity of CSNPs against Pseudomonas aeruginosa at different pH was tested using broth dilution method. Further assessment of antivirulence activity and sensitization of CSNPs on Pseudomonas aeruginosa were examined. RESULTS: Significant antimicrobial effects of CSNPs against Pseudomonas aeruginosa were detected at slightly acidic pH 5, whereas the activity was abolished at a pH of greater than 7. The antivirulence activity of CSNPs was then investigated and treatment with CSNPs (1000 ppm) resulted in a significant reduction or even complete inhibition of pyocyanin production by P. aeruginosa compared with untreated P. aeruginosa indicating the antivirulence activity of CSNPs. CSNPs also sensitized P. aeruginosa to the lytic effects of sodium dodecyl sulfate (SDS); such sensitization was not blocked by washing chitosan-treated cells prior to SDS exposure revealing that CSNPs disturb the outer membrane leading to irreversible sensitivity to detergent even at low concentration (100 ppm). CONCLUSIONS: These findings highlight CSNPs as potentially useful as indirect antimicrobial agents for a variety of applications.