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.

A novel series of 1,2,3-triazole/chalcone hybrids 6a– n was designed and synthe-
sized using a molecular hybridization approach to develop a new cytotoxic agent
capable of targeting epidermal growth factor receptor (EGFR) and/or BRAF. The
antiproliferative effect of the novel hybrids was investigated against four cancer
cells using doxorubicin as a reference. Hybrids 6a, 6d, 6f– h, and 6n have the
highest antiproliferative activity (IC50 values 0.95–1.80 μM) compared to doxoru-
bicin (IC50 1.14 μM). The most potent antiproliferative derivative, compound 6d,
was also the most potent EGFR inhibitor with an IC50 of 0.09 ± 0.05 μM, which
is comparable to the reference Erlotinib (IC 50 = 0.05 ± 0.03 μM). 6d has modest
BRAF inhibitory action with an IC50 of 0.90 ± 0.10 μM. The findings were also
related to molecular docking studies, which provided models of strong interac-
tions with the EGFR-TK domain for the inhibitors. In cell cycle analysis, hybrid
6d caused a cell cycle arrest at the G1 transition phase.

Thiourea derivatives of uracil were efficiently synthesized via the reaction of 5-
aminouracil with isothiocyanates. Then, we prepared uracil-containing
thiazoles via condensation of thioureas with diethyl/dimethyl
acetylenedicarboxylates. The structures of the products were confirmed by a
combination of spectral techniques including infra-red (IR), nuclear magnetic
resonance (NMR), mass spectrometry (MS) and elemental analyses. A rationale
for the formation of the products is presented. The newly synthesized
compounds were evaluated for their in vitro antiproliferative activity against
four cancer cell lines. The compounds tested showed promising
antiproliferative activity, with GI50 values ranging from 1.10 μM to 10.00 μM.
Compounds 3c, 5b, 5c, 5h, 5i, and 5j were the most potent derivatives, with GI50
values ranging from 1.10 μM to 1.80 μM. Compound 5b showed potent
inhibitory activity against EGFR and BRAFV600E with IC50 of 91 ± 07 and 93 ±
08 nM, respectively, indicating that this compound could serve as a dual
inhibitor of EGFR and BRAFV600E with promising antiproliferative properties.
Docking computations revealed the great potency of compounds 5b and 5j
towards EGFR and BRAFV600E with docking scores of −8.3 and −9.7 kcal/mol
and −8.2 and −9.3 kcal/mol, respectively.

A series of new 1,3,4‐oxadiazole‐chalcone/benzimidazole hybrids 9a–o and 10a–k were designed and synthesized as potential antiproliferative agents. Hybrids 9a–o exhibited remarkable antiproliferative activities on different NCI‐60 cell lines in a single‐dose assay. The antiproliferative activities of the newly synthesized
compounds were evaluated against a panel of four human cancer cell lines
(A‐549, MCF‐7, Panc‐1, and HT‐29). Compounds 9g–i and their oxygen isosteres,
10f–h, exhibited promising antiproliferative activities with IC50 values ranging from
0.80 to 2.27 μM compared to doxorubicin (IC50 ranging from 0.90 to 1.41 μM).
Furthermore, the inhibitory potency of these compounds against the epidermal
growth factor receptor (EGFR) and BRAFV600E kinases was evaluated using erlotinib
as a reference drug. Molecular modeling studies were done to investigate the
binding mode of the most active hybrids in the ATP binding site of EGFR.

Some cyclooxygenase (COX)‐2 selective medications were withdrawn from the
market just a few years after their production due to cardiovascular side effects. In
this study, a new series of pyrimidine/thiazole hybrids 7a–p was synthesized as
selective COX‐2/soluble epoxide hydrolase (sEH) inhibitors with analgesic and antiinflammatory
effects, and lower cardiotoxicity effects. The target compounds were
synthesized and in vitro tested against COX‐1, COX‐2, and sEH enzymes. Hybrids 7j,
7k, and 7i showed the greatest COX‐2‐inhibitory activity and were discovered to be
the most potent dual COX‐2/sEH inhibitors. In vivo tests revealed that these hybrids
were the most active analgesic/anti‐inflammatory agents, with improved ulcerogenic
and cardioprotective properties. Finally, the most active dual inhibitors were docked
into COX‐2/sEH active regions to explain their binding mechanisms.

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 minimal inhibitory concentration (MIC)
assays, compound 17 outperformed ciprofloxacin against E. coli, with an MIC of
55 ng/ml, compared to 60 ng/ml for ciprofloxacin. Finally, the docking study, along
with the in vitro experiments, supports our promising approach to effectively
develop potent leads for further optimization as dual DNA gyrase and Topo IV
inhibitors.