Exploiting gelatin nanocarriers in the pulmonary delivery of methotrexate for lung cancer therapy.

Gelatin has many merits that encourage its use in the pulmonary delivery of anticancer drugs. It is a biodegradable denatured protein which possesses several functional groups that could be modified. Additionally, it has balanced hydrophilic and hydrophobic characters, which facilitate the loading of chemotherapeutic agents. Accordingly, the purpose of the current work was to exploit this valuable biomaterial in the efficient pulmonary delivery of methotrexate in case of lung cancer. Gelatin nanoparticles were prepared via a desolvation method and the fabrication process was optimized using Box Behnken design of experiment. A comparative study on uptake of gelatin nanoparticles by lung adenocarcinoma cells and macrophages was implemented using flow cytometry. Investigation of the effect of different methotrexate loading techniques: encapsulation, post loading and chemical conjugation on the nanoparticles characteristics and cellular cytotoxicity was performed. Nano-in-microparticles were prepared by co-spray drying optimized nanoparticles with leucine. Results showed that Box Behnken design was able to optimize preparation parameters to yield uniform nanoparticles with suitable particle size for cancer cells uptake. The prepared nanoparticles demonstrated a preferential uptake by lung cancer cells. Additionally, methotrexate loaded nanoparticles demonstrated up to four fold significant reduction in methotrexate IC50. The spray dried gelatin nano-in microparticles demonstrated good aerosolization properties enabling lung deposition in the respirable airways. Thus, providing a promising platform for lung cancer therapy

Acute mercury toxicity modulates cytochrome P450, soluble epoxide hydrolase and their associated arachidonic acid metabolites in C57Bl/6 mouse heart

Mercury exposure is associated with increased risk of cardiovascular disease and profound cardiotoxicity. However, the correlation between Hg2+-mediated toxicity and alteration in cardiac cytochrome P450s (Cyp) and their dependent arachidonic acid metabolites has never been investigated. Therefore, we investigated the effect of acute mercury toxicity on the expression of Cyp-epoxygenases and Cyp-?-hydroxylases and their associated arachidonic acid metabolites in mice hearts. In addition, we examined the expression and activity of soluble epoxide hydrolase (sEH) as a key player in arachidonic acid metabolism pathway. Mercury toxicity was induced by a single intraperitoneal injection (IP) of 2.5mg/kg of mercuric chloride (HgCl2). Our results showed that mercury treatment caused a significant induction of the cardiac hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP); in addition to Cyp1a1, Cyp1b1, Cyp2b9, Cyp2b10, Cyp2b19, Cyp2c29, Cyp2c38, Cyp4a10, Cyp4a12, Cyp4a14, Cyp4f13, Cyp4f15, Cyp4f16 and Cyp4f18 gene expression. Moreover, Hg2+ significantly increased sEH protein expression and activity levels in hearts of mercury-treated mice, with a consequent decrease in 14,15-, and 11,12-epoxyeicosatrienoic acids (EETs) levels. Whereas the formation of 14,15-, 11,12-, 8,9-dihydroxyeicosatrienoic acids (DHETs) was significantly increased. In conclusion, acute Hg2+ toxicity modulates the expression of several Cyp and sEH enzymes with a consequent decrease in the cardioprotective EETs which could represent a novel mechanism by which mercury causes progressive cardiotoxicity. Furthermore, inhibiting sEH might represent a novel therapeutic approach to prevent Hg2+-induced hypertrophy.Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant RGPIN 250139 to A.O.S. I.E.A is the recipient of Libyan Government Scholarship. O.H.E. is the recipient of Alberta Cancer Foundation Graduate Studentship Award and Alberta Innovates Technology Futures Scholarship.Scopu

Mitigation plan and water harvesting of flashflood in arid rural communities using modelling approach: A case study in Afouna village, Egypt

This paper aims to propose methods to mitigate the risks of flash flood events in arid rural communities with poor infrastructure. A flash flood management case study was conducted at Afouna Village in Egypt, which is characterized by an arid climate and faced a devasting flash flood in 2015. First, the flash flood was modelled and it was found that it corresponds to a 100 year return period flood that led to an almost 13 million m3 total runoff volume. A structural protection approach, using an artificial infiltration pond, was applied to mitigate the flooding risks through water harvesting and recharging the groundwater of the Moghra aquifer. In this study, a novel approach was proposed, which is substituting the low permeability silty sand (2.0 × 10−4 m/s) in the pond area with a high permeability one (9.6 × 10−3 m/s), which will enhance water harvesting and reduce direct evaporation. Modern techniques of hydrological modelling were utilized in order to achieve the optimal use, and harvesting, of flash flood water