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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.

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BACKGROUND: Streptococcus pneumoniae remains a major cause of community-acquired pneumonia, meningitis, and other diseases, contributing significantly to high morbidity and mortality worldwide. Although it responds to antibiotics, their use is becoming limited due to the rise in antibiotic resistance, which necessitates the development of new therapeutics. Nanotechnology is used to counteract antimicrobial resistance. In this regard, polymeric nanoparticles (NPs) made of natural, biodegradable, biocompatible, and cationic polymers such as Chitosan (CNPs) exhibit wide-spectrum antimicrobial activity. Therefore, this study aimed to prepare CNPs, characterize their physiochemical characteristics: particle size (PZ), polydispersity index (PDI), and zeta potential (ZP), and investigate their antimicrobial activity against Streptococcus pneumoniae TIGR4 (virulent serotype 4) and its capsular mutant (∆cps). METHODS: CNPs were prepared at 1, 2.5, and 5 mg/mL concentrations using the ion gelation method. Then, PZ, PDI, and ZP were characterized using a Zetasizer. Transmission electron microscopy (TEM) was used to visualize the CNP's morphology. Broth and agar dilution methods were used to assess their antimicrobial activity. Cytotoxicity of prepared NPs on A549 cells and their effect on pneumococcal hemolysis were also investigated. RESULTS: Spherical CNPs were produced with PZ ranging from 133.3 nm ± 0.57 to 423 nm ± 12.93 PDI < 0.35, and ZP from 19 ± 0.115 to 27 ± 0.819. The prepared CNPs exhibited antibacterial activity against TIGR4 and its capsule mutant with a minimum inhibitory concentration (MIC90) of 0.5 to 2.5 mg/mL in a non-acidic environment. The hemolysis assay results revealed that CNPs reduced bacterial hemolysis in a concentration-dependent manner. Their mammalian cytotoxicity results indicated that CNPs formed from low concentrations of Chitosan (Cs) were cytocompatible. CONCLUSION: Nanochitosan particles showed anti-pneumococcal activity regardless of the presence of capsules. They resulted in a concentration-dependent reduction in bacterial hemolysis and were cytocompatible at a lower concentration of Cs. These findings highlight the potential of CNPs in the treatment of pneumococcal diseases.

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PURPOSE: The emergence of Neisseria gonorrhoeae strains that are resistant to the most commonly used antibiotics represents a great concern for global public health. This challenges the effectiveness of clinical treatment regimens and demands the development of alternative antigonococcal agent. In this regard, chitosan nanoparticles (CNPs) are known to have antimicrobial activity against a wide range of pathogens. Thus, they have become a potential candidate for combatting this era of multi-drug resistance. This study aims to formulate CNPs, characterize their physicochemical properties, and examine their antimicrobial activity against gonococcus. MATERIALS AND METHODS: The ionic gelation method was used to prepare CNPs of different concentrations. Characterization for their particle size (PZ), polydispersity index (PDI), and zeta potential (ZP) was performed. The anti-microbial activity of CNPs was investigated against 13 WHO N. gonorrhoeae reference strains, using the broth dilution method. Cytotoxicity of CNPs and their effect on bacterial adhesion to HeLa cells were investigated. RESULTS: The average PZ and ZP of the prepared NPs were increased when the concentration of chitosan was increased from 1 to 5 mg/mL and found to be in the range of 193 nm ± 1.9 to 530 nm ± 13.3, and 14 mV ± 0.5 to 20 mV ± 1, respectively. Transmission electron microscopes (TEM) images revealed spherical NPs, and the NPs had a low PDI value of ≤0.27. The formed CNPs produced antibacterial activity against all tested strains, including those resistant to multiple antibiotics, with a minimum inhibitory concentration (MIC90) of 0.16 to 0.31 mg/mL and a minimum bactericidal concentration (MBC) of 0.31 to 0.61 mg/mL. Of note, at all MIC90 and MBC, the CNPs had no significant cytotoxic effect on HeLa cells and reduced bacterial adhesion to these cells at MBC doses. CONCLUSION: The present work findings suggest the potential of the CNPs for the treatment of gonorrhoea.

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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.

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The needs for safe, therapeutically effective antidiarrheal combination continuously lead to effective treatment. When administered simultaneously, metronidazole-kaolin interactions have been reported by FDA but not studied. This paper is the first to study metronidazole-kaolin interactions. Adsorption isotherms of a metronidazole-kaolin antidiarrheal combination from aqueous solutions at an in vivo simulated pH conditions were obtained at 37 ± 0.5 °C. Langmuir constants for the adsorption are 10.8225, 41.3223 mg g(-1) and 11.60, 2.56 l g(-1) aimed at the monolayer capacity, and the equilibrium constant at pH 1.2 and 6.8, respectively. pH effect on adsorption of known concentration of metronidazole by kaolin was also studied over the range 1.2-8. A gradual increase in the adsorbed amount was noted with increasing the pH. Elution studies by different eluents showed that drug recovery from adsorbent surface was pH-dependent via competitive mechanism. The elution followed the sequence: 0.1 M HCl > 0.1 M NaCl > H2O. Adsorption-desorption studies revealed physical adsorption. The equilibrium concentration of metronidazole decreased as the adsorbent concentration was increased in the systems. The dissolution profiles (USP) of commercially available tablets (Riazole® 500 mg) were obtained alone and in the presence of either (ORS®) rehydration salts and 9 or 18 g of kaolin powder. The percentage drug released versus time: 95.01% in 25 min, 101.02% in 30 min, 67.63% in 60 min, 60.59% in 60 min, respectively. The percentage drug released versus time was increased with ORS® due to common ion effect [Cl(-)], while, it was decreased with kaolin due to adsorption. The mechanism of reaction of Riazole® (500 mg) tablets in the different dissolution media, confirms with Korsmeyer-Peppas model. The interaction between metronidazole and kaolin was characterized by melting point determinations, differential scanning calorimetry analysis and infrared spectroscopy. The results obtained were suggestive of physical interaction between metronidazole and kaolin.