AIMS: Drug delivery to the brain is hindered by the blood-brain-barrier (BBB) that filters out most of drugs after systemic administration. Therefore, there is an urgent need to develop more efficient drug delivery systems to deliver pharmaceuticals to brain. In this work, the distribution and the effect of Thymoquinone (TQ) on different oxidative stress biomarkers in different brain areas, either in the free form or encapsulated in mesoposrous silica nanocarriers (MSNs) were systematically studied.

MATERIALS AND METHODS: MSNs and Thymoquinone-loaded mesoporous silica nanoparticles (MSN-TQ) were prepared and characterized using TEM, DLS, and zeta potential. The encapsulation efficiency and release profile of MSN-TQ were investigated as well. The chromatographic quantification of TQ was carried out to evaluate the effect of TQ loading in MSNs on the TQ distribution throughout different brain regions. Additionally, some oxidative stress biomarkers were evaluated like: glutathione reduced (GSH), glutathione-s-transferase (GST), nitric acid (NO) and malondialdehyde (MDA).

KEY FINDINGS: Results showed that the encapsulation of TQ in MSNs enhanced its delivery to some brain areas (cortex, thalamus, hypothalamus and midbrain), on the other hand it reduced its delivery to the cerebellum while its delivery to medulla and striatum was not changed compared to free TQ. Neither free TQ nor MSN-TQ were able to reach the hippocampus.

SIGNIFICANCE: It was found that the encapsulation of TQ in MSNs resulted in its redistribution in different brain areas, thus, MSNs could be potentially utilized as a drug delivery system for selectively targeting the drug to certain brain areas.

Pancreatic cancer (PC) frequency and incidence have grown rapidly in recent years. One of the most serious problems with PC is the existence of asymptotic manifestations, which frequently delays early detection, and until the diagnosis is established, tumor cells progress to the metastatic stage. Another significant concern with PC is the scarcity of well-defined pharmacotherapeutic drugs. The aim of this study was to develop an efficient nanocarrier system to augment the efficacy of raloxifene (RLX) against PC cells. As a result, the current investigation was carried out in order to give an effective treatment method, in which an optimum RLX loaded phospholipid-based vesicles with melittin (PL-MEL) was chosen using experimental design software, with particle size, zeta potential and entrapment efficiency % as dependent variables. Furthermore, anticancer activity against PANC1 cells was assessed. The optimized nanovesicle parameters were 172.5 nm for the measured size, zeta potential of -0.69 mV, and entrapment efficiency of 76.91% that were in good agreement with the expected ones. RLX-raw, plain formula, and optimized RLX-PL-MEL showed IC concentrations of 26.07 ± 0.98, 9.166 ± 0.34, and 1.24 ± 0.05 µg/mL, respectively. Furthermore, cell cycle analysis revealed that the nanovesicle was most effective in the G2-M phase, whereas Bax, and Bcl-2 estimates revealed that optimized RLX formula had the highest apoptotic activity among treatments investigated. However, as compared to RLX alone or plain formula alone, the optimized formula demonstrated higher expression of TNFα and Bax while a significant reduction of Bcl-2 and NF-κB expression was observed. mitochondrial membrane potential (MMP) analysis confirmed the apoptosis as well as the anticancer effect of the optimized formula. Thus, the present study results showed an improvement in the anti-PC effects of the RLX with phospholipid conjugated melittin, making it a novel treatment approach against PC.

Cryptosporidium species are related to protozoan parasites that infect the gastrointestinal tract
of a wide variety of animals, including humans. The host immune status is crucial for determi-
ning the susceptibility to infection, the outcome and the severity of the disease. Nitazoxanide®
is the only FDA approved drug to treat such opportunistic infection, yet demonstrates limited
and immune-dependent efficacy. The present work studied the effect of combination therapy in
treating cryptosporidiosis, plus exploring the possible modulating effect on the local adaptive
immune response in experimental dexamethasone immunocompromized mice model. The re-
sults showed that combination of selenium supplementation with ivermectin® or nitazoxanide
improved the oocysts reduction percentage compared to groups receiving single anti-parasitic
therapeutic drugs alone. Also, combination of ivermectin with nitazoxanide gave the best oo-
cysts reduction rates with the lowest score of ileitis severity. But, local expression of CD4 T
cells was down-regulated and unlikely could not be elevated enough even after all treatment
types. CD8 was up regulated in all treated groups as compared with non-treated control group,
indicating its possible role in reducing the serious threats of such opportunistic infection.
Keywords: Cryptosporidium- single therapy- combined therapies- CD4- CD8.

Pomegranate (Punica granatum) is an ancient perennial plant species of the Punicaceae family and is regarded as the 'miracle fruit' for its seeds being consumed as food, juice and as a functional food. Significant modern pharmacological and clinical evidence has highlighted the wide medicinal applications of pomegranate fruit parts and its juice. Pomegranate juice (PJ) that is superior to other fruit juices is a fortified source of dietary polyphenols with potential antioxidant capacity. Polyphenols of PJ include tannins, anthocyanins, and flavonoids. The presence of these beneficial phytochemicals is directly linked to its favourable health benefits viz., obesity and diabetes management and anti-inflammatory effects. This comprehensive review capitalizes on PJ with emphasis on the interrelationship between its holistic chemical composition, metabolism and biological effects. Moreover, the review recapitulates on the diverse health benefits of PJ and related patents in the field of PJ production to ensure the best produced juice quality.