A series of hybridized pyrrolidine compounds with a 1,2,4‐oxadiazole moiety were synthesized to develop effective molecules against the enzymes DNA gyrase and topoisomerase IV (Topo IV). Compounds 8–20 were developed based on a previously disclosed series of compounds from our lab, but with small structural modifications in the hopes of increasing the compounds' biological activity. In comparison to novobiocin, with IC₅₀ = 170 nM, the findings of the DNA gyrase inhibitory assay revealed that compounds 16 and 17 were the most potent of all synthesized derivatives, with IC₅₀ values of 180 and 210 nM, respectively. Compound 17 had the strongest inhibitory effect against Escherichia coli Topo IV of all the synthesized compounds, with an IC₅₀ value of 13 µM, which was comparable to novobiocin (IC₅₀ = 11 µM). Therefore, hybrids 16 and 17 appeared to be potential dual‐target inhibitors. In the …

Throughout decades, the intrinsic power of the immune system to fight pathogens has inspired researchers to develop techniques that enable the prevention or treatment of infections via boosting the immune response against the target pathogens, which has led to the evolution of vaccines. The recruitment of Lipid nanoparticles (LNPs) as either vaccine delivery platforms or immunogenic modalities has witnessed a breakthrough recently, which has been crowned with the development of effective LNPs-based vaccines against COVID-19. In the current article, we discuss some principles of such a technology, with a special focus on the technical aspects from a translational perspective. Representative examples of LNPs-based vaccines against cancer, COVID-19, as well as other infectious diseases, autoimmune diseases, and allergies are highlighted, considering the challenges and promises. Lastly, the key features that can improve the clinical translation of this area of endeavor are inspired.

Tumor necrosis factor (TNF-α) and inflammatory cytokine (IL-6) play a vital role in various cellular incidents such as the proliferation and death of cells during carcinogenesis. Hence, regulation of these biomarkers could be a promising tool for controlling tumor progression using nanoformulations. Silver nanoparticles-poly (vinyl pyrrolidone) (AgNPs-PVP) were prepared using the reduction of silver nitrate and stabilized with PVP. They are characterized through yield percentage, UV-VIS, FT-IR, size, charge, and morphology. The obtained AgNPs were tested for anticancer activity against prostate cancer (PC 3) and human skin fibroblast (HFS) cell lines. Moreover, biomarker-based confirmations like TNF-α and IL-6 were estimated. The synthesized AgNPs-PVP were stable, spherical in shape, with particle sizes of 122.33 ± 17.61 nm, a polydispersity index of 0.49 ± 0.07, and a negative surface charge of −19.23 ± 0.61 mV. In vitro cytotoxicity testing showed the AgNPs-PVP exhibited antiproliferation properties in PC3 in a dose-dependent manner. In addition, when compared to control cells, AgNPs-PVP has lower TNF-α with a significant value (); the value reached 16.84 ± 0.71 pg/ml versus 20.81 ± 0.44 pg/ml, respectively. In addition, HSF cells showed a high level of reduction () in IL-6 production. This study suggested that AgNPs-PVP could be a possible therapeutic agent for human prostate cancer and anti-IL-6 in cancerous and noncancerous cells. Further studies will be performed to investigate the effect of AgNPs-PVP in different types of cancer.

Urinary catheter infections remain an issue for many patients and can complicate their health status, especially for individuals who require long-term catheterization. Catheters can be colonized by biofilm-forming bacteria resistant to the administered antibiotics. Therefore, this study aimed to investigate the efficacy of silver nanoparticles (AgNPs) stabilized with different polymeric materials generated via a one-step simple coating technique for their ability to inhibit biofilm formation on urinary catheters. AgNPs were prepared and characterized to confirm their formation and determine their size, charge, morphology, and physical stability. Screening of the antimicrobial activity of nanoparticle formulations and determining minimal inhibitory concentration (MIC) and their cytotoxicity against PC3 cells were performed. Moreover, the antibiofilm activity and efficacy of the AgNPs coated on the urinary catheters under static and flowing conditions were examined against a clinical isolate of Escherichia coli. The results showed that the investigated polymers could form physically stable AgNPs, especially those prepared using polyvinyl pyrrolidone (PVP) and ethyl cellulose (EC). Preliminary screening and MIC determinations suggested that the AgNPs-EC and AgNPs-PVP had superior antibacterial effects against E. coli. AgNPs-EC and AgNPs-PVP inhibited biofilm formation to 58.2% and 50.8% compared with AgNPs-PEG, silver nitrate solution and control samples. In addition, coating urinary catheters with AgNPs-EC and AgNPs-PVP at concentrations lower than the determined IC50 values significantly (p < 0.05; t-test) inhibited bacterial biofilm formation compared with noncoated catheters under both static and static and flowing conditions using two different types of commercial Foley urinary catheters. The data obtained in this study provide evidence that AgNP-coated EC and PVP could be useful as potential antibacterial and antibiofilm catheter coating agents to prevent the development of urinary tract infections caused by E. coli.

The study aims to assess the interaction between fluconazole and sulfonatocalix[4]naphthalene towards enhancing its dissolution performance and antimycotic activity. A solubility study was carried out at different pH conditions, and the results revealed the formation of a 1:1 molar ratio fluconazole-sulfonatocalix[4]naphthalene inclusion complex with an A_L type phase solubility diagrams. The solid powder systems of fluconazole-sulfonatocalix[4]naphthalene were prepared using kneaded and co-evaporation techniques and physical mixtures. DCS, PXRD, TGA-DTG, FT-IR, and in vitro dissolution performance characterize the prepared systems. According to physicochemical characterization, the co-evaporation approach produces an amorphous inclusion complex of the drug inside the cavity of sulfonatocalix[4]naphthalene. The co-evaporate product significantly increased the drug dissolution rate up to 93 ± 1.77% within 10 min, unlike other prepared solid powders. The antimycotic activity showed an increase substantially (p ≤ 0.05, t-test) antimycotic activity of fluconazole co-evaporate mixture with sulfonatocalix[4]naphthalene compared with fluconazole alone against clinical strains of Candida albicans and Candida glabrata. In conclusion, sulfonatocalix[4]naphthalene could be considered an efficient complexing agent for fluconazole to enhance its aqueous solubility, dissolution performance, and antimycotic activity.

Despite the massive advancements in the nanomedicines and their associated research, their translation into clinically-applicable products is still below promises. The latter fact necessitates an in-depth evaluation of the current nanomedicines from a clinical perspective to cope with the challenges hampering their clinical potential. Quantum dots (QDs) are semiconductors-based nanomaterials with numerous biomedical applications such as drug delivery, live imaging, and medical diagnosis, in addition to other applications beyond medicine such as in solar cells. Nevertheless, the power of QDs is still underestimated in clinics. In the current article, we review the status of QDs in literature, their preparation, characterization, and biomedical applications. In addition, the market status and the ongoing clinical trials recruiting QDs are highlighted, with a special focus on the challenges limiting the clinical translation of QDs. Moreover, QDs are technically compared to other commercially-available substitutes. Eventually, we inspire the technical aspects that should be considered to improve the clinical fate of QDs.

The preparation technique of silver nanoparticles (AgNPs) is essential for the efficient drug delivery system. AgNPs coated PEG were prepared and investigated to control NPs physicochemical characteristics as well as a selective delivery of doxorubicin (DOX) to the affected site with lower side effects. In this context, AgNPs chemically synthesized and coated with PEG having different molecular weights via two different methods. The optimized AgNPs-PEG were further loaded with DOX. The prepared particles were characterized for their size, shape, and DOX in vitro release in phosphate buffer of two pH conditions 5.0 and 7.4. Moreover, the cytotoxicity of the prepared nanoformulations was investigated against MCF-7 and HepG2 cell lines, also the biodistribution of AgNPs was also investigated in rats. It was found that the investigated two methods for AgNPs-PEG preparation did not show a significant difference on the AgNPs characteristics. The prepared AgNPs were spherical in shape and showed mono-dispersibility distribution with encapsulation efficiency percent approximately 95%. DOX showed higher release in pH 5.0 than that observed in pH 7.4. Moreover, the prepared system showed sustained release behavior compared to the unloaded DOX. AgNPs loaded with DOX significantly reduced the IC_50% compared with AgNPs-PEGs and unloaded DOX against both MCF-7 and HepG2 cell lines. In addition, biodistribution study revealed the higher accumulation of AgNPs-PEG in liver compared to the other investigated organs. It could be concluded that the optimized AgNPs-PEG could be considered as an efficient carrier for DOX with high drug loading, sustained DOX delivery, higher synergistic cytotoxicity, and lower side effects on the other healthy cells.

There are challenges to implementing high-speed direct compression tableting for poor flow, low-density cohesive powder. Thus, excipients with adequate flowability and bulk density are desired to facilitate this process. As a major novelty, the effect of nano-sized silica (Aerosil 200®) on the extent of flow and packing properties enhancement was evaluated. A 3² full-factorial design was applied to investigate the influence of silica load (X1; 0.5–5%) and mixing time (X2; 1–10 min) as independent variables on flow, bulk density and compaction properties of microcrystalline cellulose (MCC). Optimized MCC-silica blend was subsequently used in tableting of Albuterol Sulphate as a model low-dose drug. Regression analysis demonstrated significant (p ≤ 0.05) effect of X1 and X2 on tableting properties of MCC with pronounced effect of X1. Besides, nano-sized silica exhibited a significant improve in flowability, bulk density and compaction properties of MCC. However, at higher silica loading (over 2.75%) a reduction in flow and compaction was observed. The superior performance of MCC was achieved at silica load of (2.40%) and mixing time of (9.66 min). Moreover, the optimized blend could be directly compressed into tablets with excellent content uniformity, adequate mechanical strength, fast disintegration (63 ± 0.64 s) and dissolution (>90% after 5 min) that leads to rapid response. Ultimately, dry coating of poor flow-low density powder using nano-sized silica is a promising approach to improve the content uniformity of low-dose tablets prepared by high speed direct compression tableting.