Investigating the binding affinity, molecular dynamics, and ADMET properties of curcumin-IONPs as a mucoadhesive bioavailable oral treatment for iron deficiency anemia.

Iron deficiency anemia (IDA) is a common health issue, and researchers are interested in overcoming it. Nanotechnology green synthesis is one of the recent approaches to making efficient drugs. In this study, we modeled curcumin-coated iron oxide nanoparticles (cur-IONPs) to study their predicted toxicity and drug-likeness properties, then to investigate mucoadhesive behavior by docking cur-IONPs with two main mucin proteins in gastrointestinal tract (GIT) mucosa (muc 5AC and muc 2). Furthermore, the stability of cur-IONPs/protein complexes was assessed by molecular dynamics. Our in-silico studies results showed that cur-IONPs were predicted to be potential candidates to treat IDA due to its mucoadhesive properties, which could enhance the bioavailability, time residency, and iron absorbance through GIT, in addition to its high safety profile with high drug-likeness properties and oral bioavailability. Finally, molecular dynamic simulation studies revealed stable complexes supporting strength docking studies. Our results focus on the high importance of in-silico drug design studies; however, they need to be supported with in vitro and in vivo studies to reveal the efficacy, toxicity, and bioavailability of cur-IONPs.

Fucoidan/hyaluronic acid cross-linked zein nanoparticles loaded with fisetin as a novel targeted nanotherapy for oral cancer.

Fisetin (FS) is an anticancer drug having potential role in oral tumors management. However, its clinical application is limited due to its hydrophobicity and instability. Bioactive polymers-based nanosystems have a great potential in cancer therapy. Herein, different biopolymers were selected for their anticancer activity and targeting ability for nanoparticles preparation namely; fucoidan (FU), zein (Zn) and hyaluronic acid (HA). The selected FS-loaded cross-linked Zn nanoparticles (ZFH) which contains HA& FU for Zn nanoparticles stabilization showed the most suitable particle size (196 ± 6.53 nm), mean surface net charge (-38.8 ± 1.47 mV) and entrapment efficiency (98 ± 1.2 %). This is the first study to utilize both HA &FU not only for stabilization but also for dual targeting effect due to their targeting ability to multiple tumor targets. In-vitro anticancer activity of ZHF revealed remarkable uptake by SCC-4 cells with significant cytotoxic action. Further, ZHF was appraised using 4-nitroquinoline 1-oxide (4-NQO)-induced oral cancer in-vivo; ZHF significantly reduced OSCC-specific serum biomarkers levels, histologic tumor grade and increased caspase-3 level. Moreover, potential of destroying two key tumor regulatory cells; TECs and CSCs, was evaluated using their specific markers. The elaborated ZFH nanoparticles could be considered as promising targeted nanotherapy for oral cancer treatment with enhanced efficacy and survival rate.

Gel in core carbosomes as novel ophthalmic vehicles with enhanced corneal permeation and residence.

Carbopol is a good bio-adhesive polymer that increases the residence time in the eye. However, the effect of blinking and lacrimation still reduce the amount of polymer and the incorporated drug available for bioadhesion. Gel-core liposomes are advanced systems offering benefits making it a good tool for improved ocular drug delivery and residence time. Incorporation of carbopol in gel-core liposomes and their potential in ocular delivery have not so far been investigated. Fluconazole (FLZ) was selected as a challenging important ocular antifungal suffering from poor corneal permeation and short residence time. In this study, gel-core carbosomes have been elaborated as novel carbopol-based ophthalmic vehicles to solve ocular delivery obstacles of FLZ and to sustain its effect. Full in vitro appraisal was performed considering gel-core structure, entrapment efficiency, particle size and stability of the vesicles as quality attributes. Structure elucidation of the nanocarrier was performed using optical, polarizing and transmission electron microscopy before and after Triton-X100 addition. Ex-vivo ocular permeation and in vivo performance were investigated on male albino rabbits. Optimized formulation (CBS5) showed gel-core structure, nanosize (339.00 ±â€¯5.50 nm) and not defined before (62.00% ±â€¯1.73) entrapment efficiency. Cumulative amount of CBS5 permeated ex-vivo after 6 h, was 2.43 and 3.43 folds higher than that of conventional liposomes and FLZ suspension, respectively. In-vivo corneal permeation of CBS5 showed significantly higher AUC0-24 h (487.12 ±â€¯74.80) compared to that of FLZ suspension (204.34 ±â€¯7.46) with longer residence time in the eye lasts for more than 18 h. In conclusion, novel gel-core carbosomes could successfully be used as a promising delivery system for chronic ocular diseases.

Hyalugel-integrated liposomes as a novel ocular nanosized delivery system of fluconazole with promising prolonged effect.

Fungal infections need long-term therapy with the proper antifungal agent. Despite effectiveness, Fluconazole (FLZ) ocular delivery is constrained by limited penetration, short residence time, in addition to the common barriers of the eye. Hyalugel-integrated liposomes were designed as novel ocular delivery systems integrating hyaluronic acid (HA) inside and surrounding vesicles by a simple preparation technique. The impact of combining HA hydrogel and liposomes was investigated in a series of different formulations. Full in-vitro optimization was performed regarding; HA and FLZ concentration, entrapment efficiency, particle size and stability to select the formula with the best characteristics. Structure elucidation of gel integration was done using polarizing and transmission electron microscopes before and after Triton-X100 addition. Corneal deposition and permeation were examined ex-vivo and in-vivo on male albino rabbits. Selected formulation (HYS7) showed gel-integrated structure, nanosize (218.50±4.50nm) and % EE 42.81%±1.66. Ex-vivo cumulative corneal permeation of FLZ after 6h from HYS7, was 2.99 and 4.18 folds higher than conventional liposomes and FLZ suspension, respectively. In-vivo corneal permeation of HYS7 showed unprecedented sustained effect of FLZ reaching 24h. In conclusion, novel hyalugel-integrated liposomes significantly enhanced corneal permeability compared to conventional liposomes and FLZ suspension. They would be promising alternates for eye drops; decreasing frequency of administration and increasing patients' compliance.

Comparison of airway deposition distributions of particles in healthy and diseased workers in an Egyptian industrial site.

The objective of this study is the prediction and comparison of airway deposition patterns of an industrial aerosol in healthy workers and workers suffering from silicosis. Mass concentrations and related size distributions of particulate matter were measured in the industrial area of Samalut in Minia, Egypt. A novel stochastic lung deposition model, simulating the symptoms of silicosis by chronic bronchial (Br) obstruction and emphysema in the acinar (Ac) region, was applied to compute mass deposition fractions, deposition density, deposition rate and deposition density rate distributions in healthy and diseased workers. In the case of healthy workers, both mass deposition fractions and deposition rates are highest in the first half of the Ac region of the lung, while the corresponding deposition density and deposition density rate distributions exhibit a maximum in the large Br airways. In the case of diseased lungs, bullous emphysema causes a large deposition peak in the region of the bronchioli respiratorii. Regional mass deposition fractions adopt maximum values in the extrathoracic region, except during mouth breathing for bullous emphysema, where Ac deposition can be the most prominent. In general, lung deposition is significantly higher in diseased than in healthy lungs. Indeed, workers suffering from silicosis receive significantly higher Ac doses than healthy workers exposed to the same aerosol. Thus, this illness may progress faster if a diseased worker remains in a strongly polluted area.

Mass size distributions of elemental aerosols in industrial area.

Outdoor aerosol particles were characterized in industrial area of Samalut city (El-minia/Egypt) using low pressure Berner cascade impactor as an aerosol sampler. The impactor operates at 1.7 m(3)/h flow rate. Seven elements were investigated including Ca, Ba, Fe, K, Cu, Mn and Pb using atomic absorption technique. The mean mass concentrations of the elements ranged from 0.42 ng/m(3) (for Ba) to 89.62 ng/m(3) (for Fe). The mass size distributions of the investigated elements were bi-modal log normal distribution corresponding to the accumulation and coarse modes. The enrichment factors of elements indicate that Ca, Ba, Fe, K, Cu and Mn are mainly emitted into the atmosphere from soil sources while Pb is mostly due to anthropogenic sources.

Effect of indoor activity size distribution of (222)Rn progeny in-depth dose estimation.

In this work, the attached and unattached activity size distribution of (222)Rn progeny ((214)Bi and (218)Po) were measured indoor. The fraction of attached progeny was collected using a low-pressure Berner cascade-impactor technique. A constructed wire screen diffusion battery was used for collecting the fraction of unattached progeny. Most of the attached activities for (214)Bi progeny were associated with the aerosol particles of the accumulation mode. The active median aerodynamic diameter (AMAD) of this mode for (214)Bi was determined to be 350nm with a geometric standard division (GSD) of 3. The GSD of unattached size distributions for (218)Po was 1.3 with an active median aerodynamic diameter (AMTD) of 1.3nm. Given that dose estimation is sensitive to environmental conditions, an analytical method was introduced to compute the local energy deposition of (218)Po alpha particles in a target volume of 1µm spheres located at different depths in bronchial epithelium. While the depth-dose distributions for nuclides uniformly distributed within the epithelium were found to be practically constant with depth, they decreased in an almost linear fashion with increasing depth for nuclides on the airway surface.

Effect of site-specific bronchial radon progeny deposition on the spatial and temporal distributions of cellular responses.

Inhaled short-lived radon progenies may deposit in bronchial airways and interact with the epithelium by the emission of alpha particles. Simulation of the related radiobiological effects requires the knowledge of space and time distributions of alpha particle hits and biological endpoints. Present modelling efforts include simulation of radioaerosol deposition patterns in a central bronchial airway bifurcation, modelling of human bronchial epithelium, generation of alpha particle tracks, and computation of spatio-temporal distributions of cell nucleus hits, cell killing and cell transformation events. Simulation results indicate that the preferential radionuclide deposition at carinal ridges plays an important role in the space and time evolution of the biological events. While multiple hits are generally rare for low cumulative exposures, their probability may be quite high at the carinal ridges of the airway bifurcations. Likewise, cell killing and transformation events also occur with higher probability in this area. In the case of uniform surface activities, successive hits as well as cell killing and transformation events within a restricted area (say 0.5 mm(2)) are well separated in time. However, in the case of realistic inhomogeneous deposition, they occur more frequently within the mean cycle time of cells located at the carinal ridge even at low cumulative doses. The site-specificity of radionuclide deposition impacts not only on direct, but also on non-targeted radiobiological effects due to intercellular communication. Incorporation of present results into mechanistic models of carcinogenesis may provide useful information concerning the dose-effect relationship in the low-dose range.

Simulation of fiber deposition in bronchial airways.

Penetration probabilities of inhaled man-made mineral fibers to reach central human airways were computed by a stochastic lung deposition model for different flow rates and equivalent diameters. Results indicate that even thick and long fibers can penetrate into the central airways at low flow rates. Deposition efficiencies and localized deposition patterns were then computed for man-made fibers with variable lengths in a three-dimensional physiologically realistic bifurcation model of the central human airways by computational fluid dynamics (CFD) techniques for characteristic breathing patterns. The results obtained for inspiratory flow conditions indicate that deposition efficiencies were highest for parallel orientation of the fibers, increasing with rising flow rate, branching angle, and fiber length at all orientations. Furthermore, deposition patterns were highly inhomogeneous and their localized distributions showed hot spots in the vicinity of the carinal ridge and at the inner sides of the daughter airways. Comparisons with other theoretical results demonstrate that the equivalent diameter concept, if including interception, presents a reasonable approximation for the parameter ranges employed in the present study.