Cubic nanoparticles as potential carriers for a natural anticancer drug: development, in vitro and in vivo characterization.

Natural compounds that elicit anticancer properties are of great interest for cancer therapy. However, the low solubility and bioavailability of these compounds limit their use as efficient anticancer drugs. To avoid these drawbacks, incorporation of these compounds into cubic nanoparticles (cubosomes) was carried out. Cubosomes containing bergapten which is a natural anticancer compound isolated from Ficus carica were prepared by the homogenization technique using monoolein and poloxamer. These cubosomes were characterized for size, zeta potential, entrapment efficiency, small angle X-ray diffraction, in vitro release, in vitro cytotoxicity, cellular uptake, and antitumor activity. Particle size of cubosomes was 220 ± 3.6 nm with almost neutral zeta potential - 5 ± 1.2 mV and X-ray measurements confirmed the existence of the cubic structure. Additionally, more than 90% of the natural anticancer drug was entrapped within the cubosomes. A sustained release over 30 h was obtained for these cubosomes. Finally, these cubosomes illustrated higher in vitro cytotoxicity and in vivo tumor inhibition compared with the free natural anticancer compound. Thus, cubosomes could be promising carriers for enhancement of antitumor efficiency of this natural compound.

Comparative study on the performance of monoolein cubic nanoparticles and trimyristin solid lipid nanoparticles as carriers for docetaxel.

Nowadays the application of lipid nanoparticles as carriers for the delivery of anticancer drugs gained great attention in cancer therapy. Solid lipid nanoparticles (SLNs) and cubic nanoparticles (cubosomes) are considered as promising carriers in cancer therapy. The comparison of these two lipid nanoparticles as efficient carriers for the anticancer drug docetaxel was our main goal in this study. Both nanoparticles were prepared by the hot melt homogenization technique followed by measurement of particle size, zeta potential, entrapment efficiency and in vitro release of docetaxel. An advanced technique has been applied to measure the release of docetaxel from these nanoparticles using small unilamellar vesicles (SUVs) as acceptor particles which resemble many compartments in our body. All prepared nanoparticles revealed a neutral zeta potential with particle sizes of about 200 nm. While SUVs showed a negative surface charge with a zeta potential of -55 mV, cubosomes showed higher entrapment efficiency and a slower docetaxel release compared to SLNs. Additionally, cubosomes improved in vitro cytotoxicity as well as the in vivo antitumor inhibition of docetaxel compared to SLNs and docetaxel solution. Overall, our results showed that incorporation of docetaxel into cubosomes could enhance its in vitro and in vivo performance compared to docetaxel incorporated into SLNs.

Ion exchange column technique as a novel method for evaluating the release of docetaxel from different lipid nanoparticles.

Lipid nanoparticles with their unique characters showed many advantages as carriers for anticancer drugs. To compare between these nanoparticles as carriers for anticancer drugs, it was important to evaluate and characterize their drug retention and release properties. In this study, ion exchange column is used as a new evaluation technique. Solid lipid nanoparticles (SLN), nanostructured lipid carrier (NLC), and cubic nanoparticles were prepared using the homogenization technique. Characterization of these nanoparticles was carried out by measuring particle size, zeta potential, and entrapment efficiency. The ion exchange column was used to evaluate docetaxel release from the different nanoparticles as donors to acceptor liposomes that mimic the cell membranes. Both populations were mixed and at different time points, separated using the columns. The amounts of docetaxel in the eluted nanoparticles and retained liposomes were calculated. The particle size of all donors was in the nanometer range with almost neutral zeta potential. The particle size of the acceptor liposomes was 135 nm with a high negative zeta potential -55 mV. Ion exchange columns showed excellent retention of the negative acceptor liposomes while less than 1% of the different donors were retained on the columns. Cubic nanoparticles showed the highest entrapment efficiency (95%) and the slowest drug transfer in comparison with SLN and NLC. In conclusion, the ion exchange column technique can be applied successfully to evaluate the release of docetaxel from the different lipid nanoparticles to acceptor liposomes. Cubic nanoparticles showed advantageous docetaxel incorporation and transfer over SLN and NLC.

Antiviral zinc oxide nanoparticles mediated by hesperidin and in silico comparison study between antiviral phenolics as anti-SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the coronavirus (COVID-19), is the virus responsible for over 69,613,607 million infections and over 1,582,966 deaths worldwide. All treatment measures and protocols were considered to be supportive only and not curative. During this current coronavirus pandemic, searching for pharmaceutical or traditional complementary and integrative medicine to assist with prevention, treatment, and recovery has been advantageous. These phytopharmaceuticals and nutraceuticals can be more economic, available, safe and lower side effects. This is in silico comparison study of ten phenolic antiviral agents against SARS-CoV-2, as well as isolation of the most active metabolite from natural sources. Zinc oxide nanoparticles (ZnO NPs) were also then prepared using these metabolite as a reducing agent. All tested compounds showed predicted anti-SARS-CoV-2 activity. Hesperidin showed the highest docking score, this leads us to isolate it from the orange peels and we confirmed its structure by conventenional spectroscopic analysis. In addition, synthesis of hesperidin zinc oxide nanoparticles was characterized by UV, IR, XRD and TEM. In vitro antiviral activity of hesperidin and ZnO NPs was evaluated against hepatitis A virus as an example of RNA viruses. However, ZnO NPs and hesperidin showed antiviral activity against HAV but ZnO NPs showed higher activity than hesperidin. Thus, hesperidin and its mediated ZnO nanoparticles are willing antiviral agents and further studies against SARS-CoV-2 are required to be used as a potential treatment.

Terezine E, bioactive prenylated tryptophan analogue from an endophyte of Centaurea stoebe.

Fungal endophytes are considered promising sources of new bioactive natural products. In this study, a Mucor sp. has been isolated as an endophyte from the medicinal plant Centaurea stoebe. Through bioactivity-guided fractionation, the isolation of the new bioactive terezine E in addition to the previously reported 14-hydroxyterezine D was carried out. The isolated compounds were fully characterised by HRESIMS and 1D and 2D NMR analyses. Both compounds exhibited potent antiproliferative activity against K-562 and HUVEC cell lines and antifungal efficacy against the tested fungal strains.

6-shogaol protects against diabetic nephropathy and cardiomyopathy via modulation of oxidative stress/NF-κB pathway.

Diabetes dramatically increases the risk of numerous heart and kidney troubles. Diabetic nephropathy (DN) and cardiomyopathy (DC) are major causes of death. The pathophysiology of DN/DC includes inflammatory and oxidative stress mechanisms. NF-κB is one of the transcription factor that mediates signal transduction processes. Nowadays, it is suggested that inhibition of NF-κB activation could delay the development of DN and DC. 6-shogaol was reported to modulate NF-κB besides its anti-oxidant and anti-inflammatory activities. Therefore, it is worth testing it against diabetic complications. Rats were divided to 4 groups: Normal control (NC), 6-shogaol (6S), diabetic control (DC), diabetic rats treated with 6-shogaol (DC+6S). BGL, BUN, serum creatinine, total urine protein, creatine kinase (CK), LDH, NO, TNF-α NF-κB were determined in serum. Heart and kidney tissues were isolated for GSH, MDA, SOD measurement and histopathology. NF-κB was estimated in kidney tissues using immunohistopathology and western blot techniques. Results showed that diabetic rats left untreated for 16 weeks showed kidney injury as evidenced from elevated BUN, serum creatinine, urine protein, TNF-α and NF-κB. Heart tissue damage was evidence from elevated CK, LDH. Diabetic rats simultaneously treated with 6-shogaol showed a protective effect on both kidney and heart as evidenced biochemically and histopathologically. Therefore, using 6-shogaol may be of value in protection against diabetic complications in kidney and heart of rats.

Botryorhodines A-D, antifungal and cytotoxic depsidones from Botryosphaeria rhodina, an endophyte of the medicinal plant Bidens pilosa.

An endophytic fungus (Botryosphaeria rhodina) was isolated from the stems of the medicinal plant Bidens pilosa (Asteraceae) that is known for its anti-inflammatory, antiseptic and antifungal effects. The ethyl acetate extract of the fungal isolate exhibits significant antifungal activity as well as potent cytotoxic and antiproliferative effects against several cancer cell lines. Activity-guided fractionation resulted in the isolation of a complex of four depsidones, botryorhodines A-D and the auxin indole carboxylic acid. Botryorhodine A and B show moderate to weak cytotoxic activities against HeLa cell lines with a CC(50) of 96.97 microM and 36.41 microM, respectively. In addition, they also show antifungal activity against a range of pathogenic fungi such as Aspergillus terreus (MIC 26.03 microM for botryorhodine A and 49.70 microM for B) and the plant pathogen Fusarium oxysporum (MIC 191.60 microM for botryorhodine A and 238.80 microM for B). A potential role of the endophyte in modulating fungal populations living within or attacking the host plant is discussed.