MitoQ and its hyaluronic acid-based nanopreparation mitigating gamma radiation-induced intestinal injury in mice: alleviation of oxidative stress and apoptosis.

Perturbations produced by ionizing radiation on intestinal tissue are considered one of highly drastic challenges in radiotherapy. Animals were randomized into five groups. The first group was allocated as control, and the second was subjected to whole body γ-irradiation (10 Gy). The third was administered HA NP (17.6 mg/kg/day; i.p.) and then irradiated. The fourth one received MitoQ (2 mg/kg/day; i.p.) and then irradiated. The last group received MitoQ/HA NP (2 mg/kg/day; i.p.) for 5 days prior to irradiation. Mice were sacrificed a week post-γ-irradiation for evaluation. MitoQ/HA NP ameliorated mitochondrial oxidative stress as indicated by rising (TAC) and glutathione peroxidase and decreasing malondialdehyde, showing its distinguished antioxidant yield. That impacted the attenuation of apoptosis, which was revealed by the restoration of the anti-apoptotic marker and lessening proapoptotic caspase-3. Inflammatory parameters dwindled via treatment with MitoQ/HA NP. Moreover, this new NP exerts its therapeutic action through a distinguished radioprotective pathway (Hmgb1/TLR-4.) Subsequently, these antioxidants and their nanoparticles conferred protection to intestinal tissue as manifested by histopathological examination. These findings would be associated with its eminent antioxidant potential through high mitochondria targeting, enhanced cellular uptake, and ROS scavenging. This research underlines MitoQ/HA NP as a new treatment for the modulation of intestinal damage caused by radiotherapy modalities.

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.

Sonographic prediction of fetal main pulmonary artery (MPA) Doppler indices of lung maturity and neonatal respiratory distress syndrome (RDS) development.

PURPOSE: The aim of this study is to highlight the predictive role of perinatal fetal main pulmonary artery (MPA) Doppler measurements in neonatal respiratory distress syndrome development. Respiratory distress syndrome (RDS) is one of the lead causes of neonatal respiratory distress as well as neonatal death. Thus, it seems logic to evaluate fetal lung maturity before labour. METHODS: The study is a prospective cohort study performed in tertiary hospital over a period of one-year duration. 70 pregnant ladies between 34 and 38 weeks of gestation were referred for fetal echo, when pregnancy was considered a high risk. A trained radiologist using dedicated ultrasound machine with updated obstetric and fetal echo software performed the fetal echo. Doppler mode and curvilinear probe of 5.7 MHz transducer. Pediatric neonatologist observed the neonatal outcome post-natally. RESULTS: A total of 70 pregnant patients with risk factors underwent fetal echo, 26/70 (37.1%) were diagnosed with RDS conforming to the neonatal criteria. The mean acceleration time/ejection time ratio (At/Et ratio) of the fetal pulmonary artery was significantly reduced in fetuses that subsequently developed RDS than those without RDS. Contrarily, the mean pulsatility index (PI), resistance index (RI), and peak systolic velocity (PSV) of the fetal pulmonary artery were significantly high in fetuses who later developed RDS than in those who did not. CONCLUSION: Fetal MPA Doppler measurements have a major role in anticipating the development of neonatal RDS in preterm and early term neonates.

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.

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.

Comparison of drug release from liquid crystalline monoolein dispersions and solid lipid nanoparticles using a flow cytometric technique.

Colloidal lipid particles such as solid lipid nanoparticles and liquid crystalline nanoparticles have great opportunities as drug carriers especially for lipophilic drugs intended for intravenous administration. In order to evaluate drug release from these nanoparticles and determine their behavior after administration, emulsion droplets were used as a lipophilic compartment to which the transfer of a model drug was measured. The detection of the model drug transferred from monoolein cubic particles and trimyristin solid lipid nanoparticles into emulsion droplets was performed using a flow cytometric technique. A higher rate and amount of porphyrin transfer from the solid lipid nanoparticles compared to the monoolein cubic particles was observed. This difference might be attributed to the formation of a highly ordered particle which leads to the expulsion of drug to the surface of the crystalline particle. Furthermore, the sponge-like structure of the monoolein cubic particles decreases the rate and amount of drug transferred. In conclusion, the flow cytometric technique is a suitable technique to study drug transfer from these carriers to large lipophilic acceptors. Monoolein cubic particles with their unique structure can be used successfully as a drug carrier with slow drug release compared with trimyristin nanoparticles.

Investigations on the transfer of porphyrin from o/w emulsion droplets to liposomes with two different methods.

CONTEXT: Due to their small particle size, colloidal fat emulsions are suitable for intravenous administration. In order to obtain information on their potential in vivo performance, it is important to find a simple and effective in vitro assay to evaluate the drug release behavior of such particles. OBJECTIVE: Two in vitro methods were studied to measure the transfer of a lipophilic model drug from colloidal o/w emulsion droplets (donor) to liposomes (acceptor), which serve as model membranes mimicking cell membranes in the body. In the first method (column method) the acceptor particles were neutral unilamellar vesicles. In the second method (MLV method), multilamellar vesicles (MLV) were used as acceptor. MATERIALS AND METHODS: The donor nanoemulsions were prepared by high pressure homogenization. Z-average particle size, polydispersity index and zeta potential were determined. RESULTS: The transfer of porphyrin was moderate to the acceptor MLV and rapid to the acceptor unilamellar vesicles. The amount of transferred porphyrin at the end of the experiment depended on the transfer method and the donor/acceptor ratio. With both acceptors the transfer of porphyrin stopped at a concentration lower than the theoretical equilibrium values. DISCUSSION: Many factors such as acceptor particle size and donor to acceptor lipid molar ratio affect the drug transfer from the donor particles to the different acceptors. CONCLUSION: Both methods seem to be suitable to study the drug transfer from such colloidal emulsion and the use of lipophilic acceptor particles is a better approach to the conditions in blood.

Comparative study on the suitability of two techniques for measuring the transfer of lipophilic drug models from lipid nanoparticles to lipophilic acceptors.

Due to their particle size in the submicrometer range, lipid nanoparticles are suitable for parenteral administration. In order to obtain information on their potential in vivo performance, a simple and effective in vitro assay to evaluate the drug release behavior of such particles is required. This study compares the use of different experimental setups for this purpose. Lipid nanoparticles from trimyristin which were loaded with fluorescent lipophilic drug models (a temoporfin and Nile red) were used as donor particles. The transfer of the two drug models to multilamellar vesicles (MLV) and emulsion droplets as lipophilic acceptor compartments was examined. The determination of the transferred substance was performed either after separation by centrifugation or by an in situ flow cytometric technique. The transfer of temoporfin was slow to the acceptor MLV and very rapid to the acceptor emulsion. With both acceptors, the transfer of temoporfin stopped at a concentration much lower than the theoretical equilibrium values. The transfer of the less lipophilic drug Nile red was very rapid to both acceptors with equilibrium concentrations close to the expected values. The transfer results of temoporfin especially to the acceptor MLV obtained with the two detection techniques were comparable while the centrifugation technique indicated an apparently higher Nile red transfer rate than the flow cytometric technique. Both techniques are equally suitable to study the transfer of temoporfin, while the flow cytometric technique is advantageous to measure the very rapid transfer of Nile red.

An approach for delineating drinking water wellhead protection areas at the Nile Delta, Egypt.

In Egypt, production has a high priority. To this end protecting the quality of the groundwater, specifically when used for drinking water, and delineating protection areas around the drinking water wellheads for strict landuse restrictions is essential. The delineation methods are numerous; nonetheless, the uniqueness of the hydrogeological, institutional as well as social conditions in the Nile Delta region dictate a customized approach. The analysis of the hydrological conditions and land ownership at the Nile Delta indicates the need for an accurate methodology. On the other hand, attempting to calculate the wellhead protected areas around each of the drinking wells (more than 1500) requires data, human resources, and time that exceed the capabilities of the groundwater management agency. Accordingly, a combination of two methods (simplified variable shapes and numerical modeling) was adopted. Sensitivity analyses carried out using hypothetical modeling conditions have identified the pumping rate, clay thickness, hydraulic gradient, vertical conductivity of the clay, and the hydraulic conductivity as the most significant parameters in determining the dimensions of the wellhead protection areas (WHPAs). Tables of sets of WHPAs dimensions were calculated using synthetic modeling conditions representing the most common ranges of the significant parameters. Specific WHPA dimensions can be calculated by interpolation, utilizing the produced tables along with the operational and hydrogeological conditions for the well under consideration. In order to simplify the interpolation of the appropriate dimensions of the WHPAs from the calculated tables, an interactive computer program was written. The program accepts the real time data of the significant parameters as its input, and gives the appropriate WHPAs dimensions as its output.

Design of national groundwater quality monitoring network in Egypt.

In the Nile Valley and Delta the protection of groundwater resources is high priority environmental concern. Many groundwater quality problems are already dispersed and may be widespread and frequent in occurrence. Examples include problems associated with the extensive application of chemical fertilizers in agricultural specially in the new reclaimed areas, leaks in sewers, septic tanks, the aggregate effects of many different points source pollution in urban areas and natural, geologically related water quality problems. A national groundwater quality monitoring has been designed and implemented based on the stepwise procedure. The national groundwater quality monitoring network is used to quantify the quality changes in long run, either caused by pollution activities or by salt water intrusion and to describe the overall current groundwater quality status on a national scale of the main aquifers. The monitoring tools and methodologies developed in this research can be used to assure protection of public health and determine the sustainability of groundwater in various purposes. This national monitoring network plays important roles for decision makers in developing the groundwater resources management plans in different aquifers systems in Egypt.