Abstract: Epigallocatechin-3-gallate (EGCG) is a pleiotropic compound with anticancer, anti-inflammatory, and antioxidant properties. To enhance EGCG anticancer efficacy, it was loaded onto gold nanoparticles (GNPs). EGCG-GNPs were prepared by a simple green synthesis method and were evaluated using different techniques. Hemocompatibility with human blood and in vivo anticancer efficacy in Ehrlich ascites carcinoma-bearing mice were evaluated. EGCG/gold chloride molar ratio had a marked effect on the formation and properties of EGCG-GNPs where well-dispersed spherical nanoparticles were obtained at a molar ratio not more than 0.8:1. The particle size ranged from ~26 to 610 nm. High drug encapsulation efficiency and loading capacity of ~93 and 32%, respectively were obtained. When stored at 4 °C for three months, EGCG-GNPs maintained over 90% of their drug payload and had small changes in their size and zeta potential. They were non-hemolytic and had no deleterious effects on partial thromboplastin time, prothrombin time, and complement protein C3 concentration. EGCG-GNPs had significantly better in vivo anticancer efficacy compared with pristine EGCG as evidenced by smaller tumor volume and weight and higher mice body weight. These results confirm that EGCG-GNPs could serve as an efficient delivery system for EGCG with a good potential to enhance its anticancer efficacy.

Abstract: Epigallocatechin-3-gallate (EGCG) is a pleiotropic compound with anticancer, anti-inflammatory, and antioxidant properties. To enhance EGCG anticancer efficacy, it was loaded onto gold nanoparticles (GNPs). EGCG-GNPs were prepared by a simple green synthesis method and were evaluated using different techniques. Hemocompatibility with human blood and in vivo anticancer efficacy in Ehrlich ascites carcinoma-bearing mice were evaluated. EGCG/gold chloride molar ratio had a marked effect on the formation and properties of EGCG-GNPs where well-dispersed spherical nanoparticles were obtained at a molar ratio not more than 0.8:1. The particle size ranged from ~26 to 610 nm. High drug encapsulation efficiency and loading capacity of ~93 and 32%, respectively were obtained. When stored at 4 °C for three months, EGCG-GNPs maintained over 90% of their drug payload and had small changes in their size and zeta potential. They were non-hemolytic and had no deleterious effects on partial thromboplastin time, prothrombin time, and complement protein C3 concentration. EGCG-GNPs had significantly better in vivo anticancer efficacy compared with pristine EGCG as evidenced by smaller tumor volume and weight and higher mice body weight. These results confirm that EGCG-GNPs could serve as an efficient delivery system for EGCG with a good potential to enhance its anticancer efficacy.

Abstract: The opposing effect of the blood-brain barrier against the delivery of most drugs warrants the need for an efficient brain targeted drug delivery system for the successful management of neurological disorders. Temazepam-loaded nanostructured lipid carriers (NLCs) have shown possibilities for enhancing bioavailability and brain targeting affinity after oral administration. This study aimed to investigate these properties for insomnia treatment. Temazepam-NLCs were prepared by the solvent injection method and optimized using a 42 full factorial design. The optimum formulation (NLC-1) consisted of; Compritol® 888 ATO (75 mg), oleic acid (25 mg), and Poloxamer® 407 (0.3 g), with an entrapment efficiency of 75.2 ± 0.1%. The average size, zeta potential, and polydispersity index were determined to be 306.6 ± 49.6 nm, -10.2 ± 0.3 mV, and 0.09 ± 0.10, respectively. Moreover, an in vitro release study showed that the optimized temazepam NLC-1 formulation had a sustained release profile. Scintigraphy images showed evident improvement in brain uptake for the oral 99mTc-temazepam NLC-1 formulation versus the 99mTc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of 99mTc-temazepam NLC-1 formulation (292.7%), compared to that of oral 99mTc-temazepam suspension. Besides, the NLC formulation exhibited a distinct targeting affinity to rat brain. In conclusion, our results indicate that the developed temazepam NLC formulation can be considered as a potential nanocarrier for brain-mediated drug delivery in the out-patient management of insomnia.

Abstract: The opposing effect of the blood-brain barrier against the delivery of most drugs warrants the need for an efficient brain targeted drug delivery system for the successful management of neurological disorders. Temazepam-loaded nanostructured lipid carriers (NLCs) have shown possibilities for enhancing bioavailability and brain targeting affinity after oral administration. This study aimed to investigate these properties for insomnia treatment. Temazepam-NLCs were prepared by the solvent injection method and optimized using a 42 full factorial design. The optimum formulation (NLC-1) consisted of; Compritol® 888 ATO (75 mg), oleic acid (25 mg), and Poloxamer® 407 (0.3 g), with an entrapment efficiency of 75.2 ± 0.1%. The average size, zeta potential, and polydispersity index were determined to be 306.6 ± 49.6 nm, -10.2 ± 0.3 mV, and 0.09 ± 0.10, respectively. Moreover, an in vitro release study showed that the optimized temazepam NLC-1 formulation had a sustained release profile. Scintigraphy images showed evident improvement in brain uptake for the oral 99mTc-temazepam NLC-1 formulation versus the 99mTc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of 99mTc-temazepam NLC-1 formulation (292.7%), compared to that of oral 99mTc-temazepam suspension. Besides, the NLC formulation exhibited a distinct targeting affinity to rat brain. In conclusion, our results indicate that the developed temazepam NLC formulation can be considered as a potential nanocarrier for brain-mediated drug delivery in the out-patient management of insomnia.

Herein, a novel and rapid fluorometric nanoprobe was constructed for quantitation of dopamine (DA) in presence of biologically interfering compounds. The nanoprobe based on synthesis of yellow emissive nitrogen doped graphene quantum dots (N@GQDs) by advanced thermal driven oxidation. After that, the synthesized N@GQDs was capped with β-cyclodextrin (β-CD), followed by interaction with pyridoxal (PYL) vitamin B6 cofactor. This interaction resulted in diminishing the yellow fluorescence of β-CD/N@GQDs, and appearance of blue emission peak at 420 nm. Upon addition of DA, the blue emission of β-CD/N@GQDs was increased after excitation at λ = 330 nm. Under optimum conditions, the nanoprobe exhibited a linear range of 0.36–400 nM with limit of detection (LOD) of 0.117 nM. In addition, the fluorescent nanoprobe shows high selectivity and can be used for detection of DA in complicated biological matrices and human serum. This strategy might provide a potential tool for clinical diagnosis and biomedical research for DA related diseases.

Herein, a novel and rapid fluorometric nanoprobe was constructed for quantitation of dopamine (DA) in presence of biologically interfering compounds. The nanoprobe based on synthesis of yellow emissive nitrogen doped graphene quantum dots (N@GQDs) by advanced thermal driven oxidation. After that, the synthesized N@GQDs was capped with β-cyclodextrin (β-CD), followed by interaction with pyridoxal (PYL) vitamin B6 cofactor. This interaction resulted in diminishing the yellow fluorescence of β-CD/N@GQDs, and appearance of blue emission peak at 420 nm. Upon addition of DA, the blue emission of β-CD/N@GQDs was increased after excitation at λ = 330 nm. Under optimum conditions, the nanoprobe exhibited a linear range of 0.36–400 nM with limit of detection (LOD) of 0.117 nM. In addition, the fluorescent nanoprobe shows high selectivity and can be used for detection of DA in complicated biological matrices and human serum. This strategy might provide a potential tool for clinical diagnosis and biomedical research for DA related diseases.

N-Formamides are important intermediates in the synthesis of many pharmacologically active compounds and are used as protecting groups for amines or as catalysts in different reactions. The current N-formylation experiment is designed as a part of an introductory organic chemistry course for undergraduate students. The experiment includes formylation of substituted aromatic amines using formic acid under solvent-free conditions. Students are introduced to laboratory safety precautions, reaction mechanism, and basic laboratory techniques such as a solvent-free reaction setup, reflux, filtration, melting point determination, yield calculation, and lab report write-up. Students synthesized four different formamides in 50–80% yield as a straightforward application of nucleophilic substitution reactions.

N-Formamides are important intermediates in the synthesis of many pharmacologically active compounds and are used as protecting groups for amines or as catalysts in different reactions. The current N-formylation experiment is designed as a part of an introductory organic chemistry course for undergraduate students. The experiment includes formylation of substituted aromatic amines using formic acid under solvent-free conditions. Students are introduced to laboratory safety precautions, reaction mechanism, and basic laboratory techniques such as a solvent-free reaction setup, reflux, filtration, melting point determination, yield calculation, and lab report write-up. Students synthesized four different formamides in 50–80% yield as a straightforward application of nucleophilic substitution reactions.

N-Formamides are important intermediates in the synthesis of many pharmacologically active compounds and are used as protecting groups for amines or as catalysts in different reactions. The current N-formylation experiment is designed as a part of an introductory organic chemistry course for undergraduate students. The experiment includes formylation of substituted aromatic amines using formic acid under solvent-free conditions. Students are introduced to laboratory safety precautions, reaction mechanism, and basic laboratory techniques such as a solvent-free reaction setup, reflux, filtration, melting point determination, yield calculation, and lab report write-up. Students synthesized four different formamides in 50–80% yield as a straightforward application of nucleophilic substitution reactions.

Herin we report the design, synthesis, full characterization and biological investigation of new 15-LOX/COX dual inhibitors based on 1,3-thiazolidin-4-one (15-lipoxygenase pharmacophore) and 1,3,4-thiadiazole (COX pharmacophore) scaffolds. This series of molecular modifications is an extension of a previously reported series to further explore the structural activity relationship. Compounds 3a, 4e, 4n, 4q, 7 and 8 capable of inhibiting 15-LOX at (2.74, 4.2, 3.41, 10.21, 3.71 and 3.36 μM, respectively) and COX-2 at (0.32, 0.28, 0.28, 0.1, 0.28 and 0.27 μM, respectively). The results revealed that binding to 15-LOX and COX is sensitive to the bulkiness of the substituents at the 5 positions. 15-LOX bind better with small substituents, while COXs bind better with bulky substituents. Compounds 3a, 4r and 4q showed comparable in vivo anti-inflammatory activity to the reference drug (celecoxib). The ulcer liability test showed no sign of ulceration which ensures the safe gastric profile. Docking study was performed to explore the possible mode of interaction of the new compounds with the active site of human 15-LOX and COX-2. This study discloses some structural features for binding to 15-LOX and COX, thus pave the way to design anti-inflammatory agents with balanced dual inhibition of these enzymes.