A Novel Alginate Film Based on Nanocoating Approach for Enteric-Release Tablets.

The objective of this study was to propose a new coating film for biodegradable polymers and environmentally friendly processing. Here, a novel implementation of solid lipid nanoparticles (SLN) into a biodegradable alginate (ALG) film composition created a new gastric-resistant film for an enteric-release tablet. Experiments were performed on a water-soluble substance (thiamine nitrate) to characterize the effects of SLN upon the addition of the ALG coating formulation. The coated tablets or cast films were characterized based on delayed-release properties, surface morphology, moisture resistance, and chemical interactions. The SLN-ALG film displayed gastric-resistant properties (< 10% drug substance dissolved at pH 1.2) and rapid disintegration in the intestinal medium (pH 6.8). Morphological analysis using a microscope and scanning electron microscope confirmed the uniformity and smoothness of the SLN-ALG film, which improved the mechanical properties of the film. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated that SLN contributed to the formation of the film, which maintained free carboxylic groups, making the SLN-ALG film a higher acid resistance, but soluble in pH 6.8 buffer. These promising results suggest a novel nanotechnology-based coating formulation for various enteric-release dosage forms. Because of their biodegradability, the proposed ingredients and processes are safe and environment-friendly.

[Involvement of older people in the processes of modern digital transformations.]

The analysis of the results of the sociological study «Digital Technologies for Tomichs¼ of the elderly, carried out in Tomsk (May, 2021) using the focus-group discussion methodology, was carried out. The study showed that many elderly citizens have no psychological readiness and sustained motivation to integrate into digital reality. Causal relationships have been identified between the multifaceted involvement of older citizens in society and their skills in mastering and using digital technologies, which make people stronger and society as a whole more inclusive in the face of the digital future. Recommendations on the involvement of older people who have an interest in promoting ideas of digital quality of life and the opportunity to use new services in the process of digital transformation as active actors for the formation of a new, attractive and safe digital future are offered.

Ilex kudingcha C.J. Tseng Mitigates Phenotypic Characteristics of Human Autism Spectrum Disorders in a Drosophila Melanogaster Rugose Mutant.

Autism spectrum disorders (ASD) have heterogeneous etiologies involving dysfunction of central nervous systems, for which no effective pan-specific treatments are available. Ilex kudingcha (IK) C.J. Tseng is a nootropic botanical used in Asia for neuroprotection and improvement of cognition. This study establishes that a chemically characterized extract from IK (IKE) mitigates behavioral traits in the Drosophila melanogaster rugose mutant, whose traits resemble human ASD, and examines possible mechanisms. IKE treatment significantly ameliorated deficits in social interaction, short-term memory, and locomotor activity in Drosophila rugose, and significantly increased synaptic bouton number of size more than 2 µm2 in the neuromuscular junctions (NMJs) of Drosophila rugose. To clarify mechanism(s) of IKE action, methylphenidate (MPH), a dopamine transporter inhibitor, was included as a reference drug in the behavioral assays: MPH significantly improved social interaction and short-term memory deficit in Drosophila rugose; administration of the dopamine D1 receptor antagonist SCH23390 and dopamine D2 receptor antagonist sulpiride reversed the ameliorative effects of both MPH and IKE on the social interaction deficits of Drosophila rugose. To extend analysis of IKE treatment to the vertebrate central nervous system, ASD-associated gene expression in mouse hippocampus was studied by RNA-seq: IKE treatment altered the expression of genes coding phosphoinositide 3-kinases/protein kinase B (PI3K-Akt), proteins in glutamatergic, dopaminergic, serotonergic, and GABAergic synapses, cAMP response element-binding protein (CREB), and RNA transporter proteins. These results provide a foundation for further analysis of IKE as a candidate for treatment of some forms of ASD.

PEGylated-Paclitaxel and Dihydroartemisinin Nanoparticles for Simultaneously Delivering Paclitaxel and Dihydroartemisinin to Colorectal Cancer.

PURPOSE: Development of a nanoplatform constructed by the PEG-dual drug conjugation for co-delivery of paclitaxel (PTX) and Dihydroartemisinin (DHA) to the tumor. METHODS: PEG was conjugated with PTX and DHA to form PTX-PEG-DHA complex as a nanocarrier. The PTX and DHA were co-encapsulated in PTX-PEG-DHA nanoparticles (PD@PPD NPs) by the emulsion evaporation method. The physicochemical properties of PD@PPD Nps were characterized, including size, zeta potential, and morphology. The drug loading capacity and entrapment efficiency, in vitro drug release at different pH conditions were also evaluated. For in vitro assessment, the effects of the NPs on HT-29 colorectal cancer cells, including intracellular uptake, cytotoxicity, and Bcl-2 protein expression were assessed. The in vivo distribution of the NPs was investigated by labelling the NPs with Cyanine 5.5 fluorophore. Finally, the antitumor efficacy of the NPs was evaluated in HT-29 tumor-bearing mice. RESULTS: The nanoparticles were formed at small size (~114 nm) and narrow distribution. The combination of PTX and DHA in the DHA-PEG-PTX nanosystems (PD@PPD) showed remarkably increased apoptosis in colorectal adenocarcinoma HT-29 cells, as compared to free drug treatment. More importantly, the PD@PPD nanoparticles exhibited significantly higher accumulation in the tumor site owing to the enhanced permeability and retention (EPR) effect, effectively restrained the tumor growth in vivo at low-dose of PTX while reducing the systemic toxicity. CONCLUSIONS: The combination of PTX and DHA in a PEG-conjugated dual-drug co-delivery system can minimize the severe side effect associated with the high-dose of PTX while enhancing the antitumor efficacy.

Wood Architecture and Composition Are Deeply Remodeled in Frost Sensitive Eucalyptus Overexpressing CBF/DREB1 Transcription Factors.

Eucalypts are the most planted trees worldwide, but most of them are frost sensitive. Overexpressing transcription factors for CRT-repeat binding factors (CBFs) in transgenic Eucalyptus confer cold resistance both in leaves and stems. While wood plays crucial roles in trees and is affected by environmental cues, its potential role in adaptation to cold stress has been neglected. Here, we addressed this question by investigating the changes occurring in wood in response to the overexpression of two CBFs, taking advantage of available transgenic Eucalyptus lines. We performed histological, biochemical, and transcriptomic analyses on xylem samples. CBF ectopic expression led to a reduction of both primary and secondary growth, and triggered changes in xylem architecture with smaller and more frequent vessels and fibers exhibiting reduced lumens. In addition, lignin content and syringyl/guaiacyl (S/G) ratio increased. Consistently, many genes of the phenylpropanoid and lignin branch pathway were upregulated. Most of the features of xylem remodeling induced by CBF overexpression are reminiscent of those observed after long exposure of Eucalyptus trees to chilling temperatures. Altogether, these results suggest that CBF plays a central role in the cross-talk between response to cold and wood formation and that the remodeling of wood is part of the adaptive strategies to face cold stress.

Development of electrosprayed artesunate-loaded core-shell nanoparticles.

OBJECTIVE: Artesunate (ART) is proven to have potential anti-proliferative activities, but its instability and poor aqueous solubility limit its application as an anti-cancer drug. The present study was undertaken to develop coaxial electrospraying as a novel technique for fabricating nanoscale drug delivery systems of ART as the core-shell nanostructures. METHODS: The core-shell nanoparticles (NPs) were fabricated with coaxial electrospraying and the formation mechanisms of NPs were examined. The physical solid state and drug-polymer interactions of NPs were characterized by X-ray powder diffraction (XRPD) and Fourier transform infrared (FTIR) spectroscopy. The effects of materials and electrospraying process on the particle size and surface morphology of NPs were investigated by scanning electron microscopy (SEM). The drug release from NPs was determined in vitro by a dialysis method. RESULTS: The ART/poly(lactic-co-glycolic) acid (PLGA) chitosan (CS) NPs exhibited the mean particle size of 303 ± 93 nm and relatively high entrapment efficiency (80.5%). The release pattern showed an initial rapid release within two hours followed by very slow extended release. The release pattern approached the Korsmeyer-Peppas model. CONCLUSIONS: The present results suggest that the core-shell NPs containing PLGA and CS have a potential as carriers in the anticancer drug therapy of ART.

Developing combination of artesunate with paclitaxel loaded into poly-d,l-lactic-co-glycolic acid nanoparticle for systemic delivery to exhibit synergic chemotherapeutic response.

OBJECTIVES: Paclitaxel (PTX) has been indicated for the treatment of a variety of solid tumors, whereas artesunate (ART) has been reported to have the potential for use in combination chemotherapy. In this study, the combination of ART and PTX was prepared in nanoparticle to induce the synergic effect and improve therapeutic efficiency in treatment of breast cancer. METHODS: Dual anticancer agents (PTX and ART) were loaded into Poly-D,L-lactic-co-glycolic acid (PLGA) nanoparticle (NP) by solvent evaporation technique from oil-in-water emulsion, stabilized with Tween 80. Physicochemical properties of obtained nanoparticles (PTX-ART-NPs) were characterized including particle size (Z), polydispersity index (PDI), zeta potentials (ZP), encapsulation efficiency (EE), and in-vitro drug release. Combination index (CI) was calculated to determine the synergic effect of the combination and select the best ratio of ART and PTX. The final NPs analyzed intracellular uptake, cytotoxicity assay, and apoptosis study. RESULTS: The final NP had a small size (around 120 nm) with a narrow size distribution (PDI <0.3). EE values for each drug were 87.8 ± 1.1% and 99.5 ± 0.1% for ART and PTX, respectively, and drugs were released from NPs in a controlled release pattern. All combinations of PTX and ART had CI values under 1, which confirmed the synergic effects. Meanwhile, NP preparation increased cytotoxicity on three breast cancer cell-lines comparable to free drugs. CONCLUSIONS: Combination of ART- and PTX-loaded PLGA NP showed promising results for anticancer therapy, especially for breast cancer treatment.

Development and Evaluation of Artesunate-Loaded Chitosan-Coated Lipid Nanocapsule as a Potential Drug Delivery System Against Breast Cancer.

Artesunate (ART)--a well-known hydrophobic anti-malarial agent was incorporated in a polymer-lipid hybrid nanocolloidal system for anti-cancer therapeutic. The lipid negatively charged nanoemulsion was formulated by modified hot homogenization method then covered with positively charged chitosan via electrostatic interaction to obtain chitosan-coated lipid nanocapsule (ART-CLN). Physical properties of the system were characterized in terms of size, charge, morphology, drug loading capacity, and physical state. In addition, anti-cancer activities were confirmed by conducting MTT assay for ART and ART-CLN on different cancer cell lines. Obtained ART-CLN after coating chitosan revealed positive charge (13.2 ± 0.87 mV), small particle size (160.9 ± 3.5 nm), and spherical shape. High drug entrapment efficiency (95.49 ± 1.13%) and sustained release pattern were observed. Moreover, the good cellular uptake was recorded by flow cytometry as well as confocal image. Finally, ART-CLN exhibited stronger anti-cancer activity than free ART on breast cancer cell lines (MCF-7, MDA-MB-231). These results suggested that by loading ART into lipid core of polymer-lipid hybrid carrier, the activity and physical stability of ART can be significantly increased for cancer chemotherapy.

Compression of coated drug beads for sustained release tablet of glipizide: formulation, and dissolution.

A promising glipizide formulation comprising compression of four-layer coated beads into tablets was prepared. The tablet offered the advantages of: a two-hour lag time before drug release, retaining sustained release characteristics and providing approximately zero-order drug release. Drug release was nearly independent of paddle speeds of 50 and 100 rpm releasing 80% over 14 h similar to the commercial glipizide osmotic pump tablet during dissolution testing while keeping the benefits of multiparticular dosage forms. The tablets contain beads with four layers: (1) the innermost layer consists of 2.5 g glipizide and 3.75 g solid ethylcellulose (Surelease®) coated onto 71.25 g of sugar beads; (2) next a hardening layer of 5 g of hypromellose; (3) the controlled release layer of 7.5 g of Surelease®:lactose at a solids ratio of 100:7 and (4) an outermost layer of 20 g of lactose:sodium starch glycolate (Explotab®) at a 2:1 ratio. Then, beads were compressed into tablets containing 11 mg of glipizide using 1500 lbs of compression pressure. The dissolution test similarity factor (f2) was above 50 for all test conditions for formulation F13 and Glucotrol® with a high of 69.9. The two Surelease® layers both aid controlling drug release, with the Surelease®-drug layer affecting drug release to a greater extent.

Hybrid Nanoparticle for Co-delivering Paclitaxel and Dihydroartemisinin to Exhibit Synergic Anticancer Therapeutics.

AIM: Anticancer treatment is required to provide effective and safe patient medicines. This research aided in developing and applying nanoparticles (NPs) for cancer treatment. BACKGROUND: The poor solubility of paclitaxel (PTX) restricts its therapeutic efficacy because of allergic side effects caused by formulation excipients. To overcome this, PTX was coupled with artemisinin derivatives and loaded into an NP drug delivery system to enhance its effects while addressing its low solubility. OBJECTIVES: This study prepared and characterized a hybrid PLGA-lecithin NP containing dihydroartemisinin (DHA) and PTX for synergic anticancer therapy. A lyophilization study improved the stability of the NP drug formulations. METHODS: Dual PTX- and DHA-loaded PLGA- and lecithin-based NPs were prepared using a single-step solvent evaporation method. The NP suspensions were lyophilized, and the types and ratios of cryoprotectants were investigated. The physicochemical properties of NPs and lyophilized cakes (Lyo-NPs) were characterized. The stability of the Lyo-NPs was investigated at 2-8°C and room conditions. The anticancer effects of the drug combination, NP suspension, and lyophilized powder were analyzed using an in vitro cytotoxicity assay and an in vivo model. RESULTS: The optimal PTX-DHA loaded PLGA-lecithin-NP was formulated (200 nm, PDI: 0.248 ± 0.003, Zeta potential: -33.60 ± 3.39 mV). Mannitol was selected for lyophilization. Lyo-NPs improved the stability of the NPs (1 year), wherein the physicochemical properties of the NPs were maintained (RDI was close to 1.0). An in-vitro cytotoxicity assay of PTX combined with DHA showed a synergistic anticancer effect (CI <1.0). The suppressive effects of Lyo-NPs on tumor growth in vivo were dose-dependent. While the cocktail of free drugs showed high toxicity (7.5 mg PTX-15 mg DHA/kg) in-vivo, Lyo-NPs showed no statistical differences in hematological and biochemical parameters compared to the control. CONCLUSION: Dual-drug-loaded hybrid PLGA-lecithin NP is a potential system to minimize severe side effects while enhancing antitumor efficacy, in which lyophilization is a key process to increase stability.

Magnetic resonance imaging-based bone imaging of the lower limb: Strategies for generating high-resolution synthetic computed tomography.

This study aims at assessing approaches for generating high-resolution magnetic resonance imaging- (MRI-) based synthetic computed tomography (sCT) images suitable for orthopedic care using a deep learning model trained on low-resolution computed tomography (CT) data. To that end, paired MRI and CT data of three anatomical regions were used: high-resolution knee and ankle data, and low-resolution hip data. Four experiments were conducted to investigate the impact of low-resolution training CT data on sCT generation and to find ways to train models on low-resolution data while providing high-resolution sCT images. Experiments included resampling of the training data or augmentation of the low-resolution data with high-resolution data. Training sCT generation models using low-resolution CT data resulted in blurry sCT images. By resampling the MRI/CT pairs before the training, models generated sharper images, presumably through an increase in the MRI/CT mutual information. Alternatively, augmenting the low-resolution with high-resolution data improved sCT in terms of mean absolute error proportionally to the amount of high-resolution data. Overall, the morphological accuracy was satisfactory as assessed by an average intermodal distance between joint centers ranging from 0.7 to 1.2 mm and by an average intermodal root-mean-squared distances between bone surfaces under 0.7 mm. Average dice scores ranged from 79.8% to 87.3% for bony structures. To conclude, this paper proposed approaches to generate high-resolution sCT suitable for orthopedic care using low-resolution data. This can generalize the use of sCT for imaging the musculoskeletal system, paving the way for an MR-only imaging with simplified logistics and no ionizing radiation.

Samae Dam Chicken: A variety of the Pradu Hang Dam breed revealed from microsatellite genotyping data.

Objective: The remarkable adaptability to the environment, high growth rate, meat with good taste and aroma, and ornamental appearance of the Pradu Hang Dam (PDH) and Samae Dam (SD) chickens make them valuable for improvement of poultry production to enhance food security. However, despite their close phenotypic similarity, distinct classification of PDH and SD chickens remains controversial. Thus, this study aimed to clarify genetic origins and variation between PDH and SD chickens, genetic diversity and structures of PDH and SD chickens. Methods: This study analyzed 5 populations of PDH and 2 populations of SD chickens using 28 microsatellite markers and compared with those of other indigenous and local chicken breeds using Thailand's "The Siam Chicken Bioresource Project" database. Results: Considerably high genetic variability was observed within PDH (370 total alleles; 4.086 ± 0.312 alleles/locus) and SD chickens (179 total alleles; 3.607 ± 0.349 alleles/locus). A partial overlap of gene pools was observed between SD chickens from the Department of Livestock, Uthai Thani (SD1) and PDH chickens, suggesting a potentially close relationship between the two chicken breeds. A gene pool that is partially overlapped with that of the red junglefowl was observed in the SD chicken population from the Sanhawat Farm Uthai Thani population (SD2). Distinct subclusters were observed within SD chickens, indicating the possibility that genetic differentiation occurred early in the process of establishment of SD chickens. Conclusion: These findings could offer valuable insights into genetic verification of Thai local chicken breeds and their sustainable conservation and utilization.

Purposive breeding strategies drive genetic differentiation in Thai fighting cock breeds.

BACKGROUND: Fighting cock breeds have considerable historical and cultural place in Thailand. Breeds such as Lueng Hang Khao (LHK) and Pradu Hang Dam (PDH) are known for their impressive plumage and unique meat quality, suggesting selection for fighting and other purposes. However, information regarding the genetic diversity and clustering in indigenous and local Thai chickens used for cockfighting is unclear. OBJECTIVE: To investigates the genetic diversity and differentiation in Thai fighting cock breeds, including populations for cockfighting, ornamental aspects, and consumption. METHODS: Thai fighting cook breeds, including LHK and PDH chickens were analyzed using genotyping with 28 microsatellite loci. Data were compared to a gene pool library from "The Siam Chicken Bioresource Project" to understand the impact of human selection on genetic differentiation. Fighting cock strains from different breeds may cluster owing to shared breeding goals. RESULT: The analysis of several chicken breeds showed subpopulation differentiation driven by artificial selection and genetic drift, affecting the genetic landscape and causing genetic hitchhiking. Eleven of 28 microsatellite loci showed hitchhiking selection, indicating directional selection in fighting cocks. Additionally, analyses revealed admixture with domestic chicken breeds and minimal influence of red junglefowl in the gene pool of Thai fighting chickens. These findings inform breed improvement, selection strategies, genetic resource management, and maintaining genetic diversity in fighting cocks. CONCLUSION: Analysis of Thai Fighting chicken breeds revealed a correlation between utilization and subpopulation differentiation. Specifically, selection for cockfighting and ornamental traits appears to explain the observed genetic structure within these breeds.

Enhancement of NH3 gas sensitivity at room temperature by carbon nanotube-based sensor coated with Co nanoparticles.

Multi-walled carbon nanotube (MWCNT) film has been fabricated onto Pt-patterned alumina substrates using the chemical vapor deposition method for NH(3) gas sensing applications. The MWCNT-based sensor is sensitive to NH(3) gas at room temperature. Nanoclusters of Co catalysts have been sputtered on the surface of the MWCNT film to enhance gas sensitivity with respect to unfunctionalized CNT films. The gas sensitivity of Co-functionalized MWCNT-based gas sensors is thus significantly improved. The sensor exhibits good repeatability and high selectivity towards NH(3), compared with alcohol and LPG.

Microneedle-Mediated Transdermal Delivery of Biopharmaceuticals.

Transdermal delivery provides numerous benefits over conventional routes of administration. However, this strategy is generally limited to a few molecules with specific physicochemical properties (low molecular weight, high potency, and moderate lipophilicity) due to the barrier function of the stratum corneum layer. Researchers have developed several physical enhancement techniques to expand the applications of the transdermal field; among these, microneedle technology has recently emerged as a promising platform to deliver therapeutic agents of any size into and across the skin. Typically, hydrophilic biomolecules cannot penetrate the skin by passive diffusion. Microneedle insertion disrupts skin integrity and compromises its protective function, thus creating pathways (microchannels) for enhanced permeation of macromolecules. Microneedles not only improve stability but also enhance skin delivery of various biomolecules. Academic institutions and industrial companies have invested substantial resources in the development of microneedle systems for biopharmaceutical delivery. This review article summarizes the most recent research to provide a comprehensive discussion about microneedle-mediated delivery of macromolecules, covering various topics from the introduction of the skin, transdermal delivery, microneedles, and biopharmaceuticals (current status, conventional administration, and stability issues), to different microneedle types, clinical trials, safety and acceptability of microneedles, manufacturing and regulatory issues, and the future of microneedle technology.

Application of Computational Screening Tools and Nanotechnology for Enhanced Drug Synergism in Cancer Therapy.

BACKGROUND: Chemoresistance continues to limit the recovery of patients with cancer. New strategies, such as combination therapy or nanotechnology, can be further improved. OBJECTIVE: In this study, we applied the computational strategy by exploiting two databases (CellMiner and Prism) to sort out the cell lines sensitive to both anti-cancer drugs, paclitaxel (PTX) and dihydroartemisinin (DHA); both of which are potentially synergistic in several cell lines. METHODS: The combination of PTX and DHA was screened at different ratios to select the optimal ratio that could inhibit lung adenocarcinoma NCI-H23 the most. To further enhance therapeutic efficacy, these combinations of drugs were incorporated into a nanosystem. RESULTS: At a PTX:DHA ratio of 1:2 (w/w), the combined drugs obtained the best combination index (0.84), indicating a synergistic effect. The drug-loaded nanoparticles sized at 135 nm with the drug loading capacity of 15.5 ± 1.34 and 13.8 ± 0.56 corresponding to DHA and PTX, respectively, were used. The nano-sized particles improved drug internalization into the cells, resulting in the significant inhibition of cell growth at all tested concentrations (p < 0.001). Additionally, α-tubulin aggregation, DNA damage suggested the molecular mechanism behind cell death upon PTX-DHA-loaded nanoparticle treatment. Moreover, the rate of apoptosis increased from approximately 5% to more than 20%, and the expression of apoptotic proteins changed 4 and 3 folds corresponding to p-53 and Bcl-2, respectively. CONCLUSION: This study was designed thoroughly by screening cell lines for the optimization of formulations. This novel approach could pave the way for the selection of combined drugs for precise cancer treatment.

Novel mesalamine-loaded beads in tablets for delayed release of drug to the colon.

Novel 'beads-in-a-tablet' formulations (total weight ∼740-780 mg) have been prepared that meet USP 31 requirements for Delayed Release of mesalamine. Several methods are presented that overcome breakage of beads during tablet compaction were explored. Bead formulations comprise a combination of extrusion and spheronization to produce a relatively high drug load (80%), followed by coating (25%) with a colonic-targeted drug release polymer (polymethacrylates, Eudragit(®) S100), overcoated (3%) with hydroxypropyl methylcellulose (Opadry(®)) to improve bead binding and compactability, and using 20% coat of lactose/sodium starch glycolate (Explotab(®)) as binder/disintegrant/cushioning agent, thus allowing a sufficiently thick coating to be uniform and without being broken during tablet compaction. Then, the aforementioned beads were compressed into tablets at 1500 pounds of pressure containing 400 mg of mesalamine, and finally coating the compressed tablets with Surelease(®) (ethylcellulose):Opadry(®) = 1:0.5 ranging from 1.5-2.5% weight gain; the resulting tablets met USP 31 dissolution requirements for delayed release tablets.

Verapamil sustained release: new formulation and convolution.

A novel bead formulation of verapamil hydrochloride was developed comprising a combination of extrusion and spheronization to produce a relatively high drug load, followed by coating of the bead with an insoluble polymer (ethylcellulose) that contains a water soluble channeling agent (lactose), thus allowing the application of a sufficiently thick outer coating that is uniform and robust without 'shutting down' release of the relatively insoluble drug. The new formulation provided the unexpected benefit that by adjusting both coating thickness and ethylcellulose/lactose ratio, it is possible to obtain essentially non-agitation sensitive and approximately zero-order drug release up to 14 hours in either KCl or two pH media, at stirring speeds of either 75 or 200 rpm with either the USP basket or USP paddle stirring method.

Numerical study of sediment scour at meander flume outlet of boxed culvert diversion work.

BACKGROUND: Sediment scour at downstream of hydraulic structures is one of the main reasons threatening its stability. Several soil properties and initial input data have been studied to investigate its influence on scour hole geometry by both physical and numerical models. However, parameters of resistance affecting sedimentation and erosion phenomena have not been carried out in the literature. Besides, the auxiliary-like wing walls prevalently used in many real applications have been rarely addressed for their effect on morphological change. RESULTS: In this study, a 3D Computational Fluid Dynamics model is utilized to calibrate the hydraulic characteristics of steady flow going through the culvert by comparison with experimental data, showing good agreement between water depth, velocity, and pressure profiles at the bottom of the boxed culvert. The results show that a grid cell of 0.015 m gave minimum NRMSE and MAE values in test cases. Another approach is numerical testing sediment scour at a meander flume outlet with a variety of roughness/d50 ratio (cs) and diversion wall types. The findings include the following: cs = 2.5 indicates the close agreement between the numerical and analytical results of maximum scour depth after the culvert; the influence of four types of wing wall on the geometrical deformation including erosion at the concave bank and deposition at the convex bank of the meander flume outlet; and two short headwalls represent the best solution that accounts for small morphological changes. CONCLUSIONS: The influence of the roughness parameter of soil material and headwall types on sediment scour at the meander exit channel of hydraulic structure can be estimated by the numerical model.

Formulation and characterization of hydroxyethyl cellulose-based gel containing metronidazole-loaded solid lipid nanoparticles for buccal mucosal drug delivery.

Local delivery of drug is a promising strategy to manage periodontitis characterized by chronic inflammation of the soft tissue surrounding the teeth. An optimized system should prolong the drug retention time and exhibit controlled drug permeation through the buccal mucosal layer. This study was aimed to develop hydroxyethyl cellulose (HEC)-based gel containing metronidazole (MTZ) loaded in solid lipid nanoparticles (SLNs), and to enhance the antimicrobial activity of MTZ. SLNs were prepared using a combination method of solvent evaporation and hot homogenization. The results showed that the fabricated SLNs, comprising of Precirol (2.93%, w/v), Tween 80 (1.8%, w/v), and the drug:lipid ratio of 19.3% (w/w), were approximately 200 nm in size, with a narrow distribution. The HEC (3%, w/w)-based gel formed a smooth, homogeneous structure and had preferable mechanical and rheological properties. Moreover, the MTZ-loaded SLNs-based HEC gel (equivalent to 1% of MTZ, w/w) exhibited a sustained in vitro drug release pattern, optimal ex vivo permeability, and enhanced in vitro antimicrobial activity after 24 h of treatment. These findings indicate the potential of the MTZ-loaded SLNs-based HEC formulation for local drug delivery at the buccal mucosa in managing periodontal disease.