No abstract

Skin is the largest mechanical barrier against invading pathogens. Following skin injury, the healing process immediately starts to regenerate the damaged tissues and to avoid complications that usually include colonization by pathogenic bacteria, leading to fever and sepsis, which further impairs and complicates the healing process. So, there is an urgent need to develop a novel pharmaceutical material that promotes the healing of infected wounds. The present work aimed to prepare and evaluate the efficacy of novel azithromycin-loaded zinc oxide nanoparticles (AZM-ZnONPs) in the treatment of infected wounds. The Box–Behnken design and response surface methodology were used to evaluate loading efficiency and release characteristics of the prepared NPs. The minimum inhibitory concentration (MIC) of the formulations was determined against Staphylococcus aureus and Escherichia coli. Moreover, the anti-bacterial and wound-healing activities of the AZM-loaded ZnONPs impregnated into hydroxyl propyl methylcellulose (HPMC) gel were evaluated in an excisional wound model in rats. The prepared ZnONPs were loaded with AZM by adsorption. The prepared ZnONPs were fully characterized by XRD, EDAX, SEM, TEM, and FT-IR analysis. Particle size distribution for the prepared ZnO and AZM-ZnONPs were determined and found to be 34 and 39 nm, respectively. The mechanism by which AZM adsorbed on the surface of ZnONPs was the best fit by the Freundlich model with a maximum load capacity of 160.4 mg/g. Anti-microbial studies showed that AZM-ZnONPs were more effective than other controls. Using an experimental infection model in rats, AZM-ZnONPs impregnated into HPMC gel enhanced bacterial clearance and epidermal regeneration, and stimulated tissue formation. In conclusion, AZM -loaded ZnONPs are a promising platform for effective and rapid healing of infected wounds.

No abstract

Colorectal cancer (CRC) is the third highest major cause of morbidity and mortality worldwide. Hence, many strategies and approaches have been widely developed for cancer treatment. This work prepared and evaluated the antitumor activity of 5-Fluorouracil (5-Fu) loaded chromium nanoparticles (5-FuCrNPs). The green biosynthesis approach using Harpullia (H) pendula aqueous extract was used for CrNPs preparation, which was further loaded with 5-Fu. The prepared NPs were characterized for morphology using scanning and transmission electron microscopes (SEM and TEM). The results revealed the formation of uniform, mono-dispersive, and highly stable CrNPs with a mean size of 23 nm. Encapsulation of 5-Fu over CrNPs, with a higher drug loading efficiency, was successful with a mean size of 29 nm being produced. In addition, Fourier transform infrared (FTIR) and X-ray diffraction pattern (XRD) were also used for the investigation. The drug 5-Fu was adsorbed on the surface of biosynthesized CrNPs in order to overcome its clinical resistance and increase its activity against CRC cells. Box–Behnken Design (BBD) and response surface methodology (RSM) were used to characterize and optimize the formulation factors (5-Fu concentration, CrNP weight, and temperature). Furthermore, the antitumor activity of the prepared 5-FuCrNPs was tested against CRC cells (CACO-2). This in vitro antitumor study demonstrated that 5-Fu-loaded CrNPs markedly decreased the IC50 of 5-Fu and exerted more cytotoxicity at nearly all concentrations than 5-Fu alone. In conclusion, 5-FuCrNPs is a promising drug delivery system for the effective treatment of CRC.

Liposomes are widely used for systemic delivery of chemotherapeutic agents to reduce their nonspecific side effects. Gemcitabine (Gem) makes a great candidate for liposomal encapsulation due to the short half-life and non-specific side effects; however, it has been difficult to achieve liposomal Gem with high drug loading capacity. Remote loading, which uses a transmembrane pH gradient to induce influx of drug and locks the drug in the core as a sulfate complex, does not serve Gem as efficiently as doxorubicin (Dox) due to the low pKa value of Gem. Existing studies have attempted to improve Gem loading capacity in liposomes by employing lipophilic Gem derivatives or creating a high concentration gradient for active loading into the hydrophilic cores (small volume loading). In this study we combine remote loading approach and small volume loading or hypertonic loading, a new approach to induce the influx of Gem into the preformed liposomes by high osmotic pressure, to achieve a Gem loading capacity of 9.4 – 10.3 wt% in contrast to 0.14 – 3.8 wt% of the conventional methods. Liposomal Gem showed a good stability during storage, sustained-release over 120 h in vitro, enhanced cellular uptake and improved cytotoxicity as compared to free Gem. Liposomal Gem showed a synergistic effect with liposomal Dox on Huh7 hepatocellular carcinoma cells. A mixture of liposomal Gem and liposomal Dox delivered both drugs to the tumor more efficiently than a free drug mixture and showed a relatively good anti-tumor effect in a xenograft model of hepatocellular carcinoma. This study shows that bioactive liposomal Gem with high drug loading capacity can be produced by remote loading combined with additional approaches to increase drug influx into the liposomes.

The narrow antibacterial spectrum of phenylthiazole antibiotics was expanded by replacing central thiazole with a pyrazole ring while maintaining its other pharmacophoric features. The most promising derivative, compound 23, was more potent than vancomycin against multidrug-resistant Gram-positive clinical isolates, including vancomycin- and linezolid-resistant methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) value as low as 0.5 μg/mL. Moreover, compound 23 was superior to imipenem and meropenem against highly pathogenic carbapenem-resistant strains, such as Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. In addition to the notable biofilm inhibition activity, compound 23 outperformed both vancomycin and kanamycin in reducing the intracellular burden of both Gram-positive and Gram-negative pathogenic bacteria. Compound 23 cleared 90% of intracellular MRSA and 98% of Salmonella enteritidis at 2× the MIC. Moreover, preliminary pharmacokinetic investigations indicated that this class of novel antibacterial compounds is highly metabolically stable with a biological half-life of 10.5 h, suggesting a once-daily dosing regimen.

No abstract

Thirty-two new naphthylthiazole derivatives were synthesized with the aim of exploring their antimicrobial effect on multidrug-resistant Gram-positive bacteria. Compounds 25 and 32, with ethylenediamine and methylguanidine side chains, represent the most promising derivatives, as their antibacterial spectrum includes activity against multidrug-resistant staphylococcal and enterococcal strains. Moreover, the new derivatives are highly advantageous over the existing frontline therapeutics for the treatment of multidrug-resistant Gram-positive bacteria. In this vein, compound 25 possesses three attributes: no bacterial resistance was developed against it even after 15 passages, it was very efficient in targeting intracellular pathogens, and it exhibited a concentration-dependent ability to disrupt the preformed bacterial biofilm.