Newly synthesized sulfonamide derivatives explored for DNA binding, enzyme inhibitory, and cytotoxicity activities: a mixed computational and experimental analyses.

The current research work reports the synthesis of three 4-((3-arylthiazolo[3,4-d]isoxazol-5-yl)amino)benzene sulfonamide derivatives with a thaizaole(3,4-d)isoxazole-based fused ring heterocyclic system. The synthesized and characterized derivatives, namely, 4-(3-(2-hydroxy-3-methoxyphenyl)thiazolo[3,4-d]soxazole-5-ylamino)benzenesulfonamide (YM-1), 4-(3-(4-chlorophenyl)isoxazolo[3,4-d]thiazol-5-ylamino)benzenesulfonamide (YM-2), and 4-(3-(3-hydroxyphenyl)isoxazolo[3,4-d]thiazol-5-ylamino)benzenesulfonamide (YM-3) were further explored for their binding interactions with DNA and enzymes (urease and carbonic anhydrase). Cytotoxicity of these derivatives for both healthy (HEK-293) and cancerous (MG-U87) cells was determined by MTT analysis. Both experimental (UV-visible, fluorescence, cyclic voltammetry, and viscometry) and theoretical (molecular docking) profiles suggested that these derivatives are good DNA binders. All the derivatives interacted with DNA via mixed intercalative and groove binding interactions. However, the evaluated DNA binding parameters (K b, ΔG, and n) were comparatively greater for YM-1. Docking data (K b and ΔG) for binding of these derivatives with enzymes also supported that YM-1 was a comparatively better inhibitor for carbonic anhydrase. However, experimentally evaluated IC50 (1.90 ± 0.02 µM) and % inhibition (57.93%) were found to be greater for YM-2 against urease enzyme. All the derivatives show dose-dependent cytotoxicity (70-90%) against MG-U87 cancer cells. Conversely, only one concentration of YM-1 (120 µM) showed less toxicity (50.28% with IC50 of 1.154 ± 0.317 µM) than that of the positive control (52.22%) for healthy cells. Overall findings suggested sulfonamide derivative YM-1 is a better candidate for DNA binding, enzyme inhibition as well as anticancer activity.

Hyaluronic acid-solid lipid nano transporter serum preparation for enhancing topical tretinoin delivery: skin safety study and visual assessment of skin.

The use of nanosized particles is becoming more popular for the topical treatment of skin conditions. In this research work, we created and investigated the effects of solid lipid nanoparticles (SLN) containing hyaluronic acid and tretinoin. Solvent emulsification diffusion method was used to prepare the SLN formulation and characterized for their physicochemical properties. Fourier transform infrared spectroscopy was used to confirm that hyaluronic acid and tretinoin were incorporated in the SLN. Furthermore, X-ray diffractogram, thermal analysis including DSC and TGA and in vitro dissolution, permeation tests were also performed along with microbial assessment. Clinical studies in human were performed to evaluate the effect of the SLN on skin wrinkles. The SLN was 750 ± 31.29 nm in size, with a zeta potential of 13.07 ± 0.75 mV and a narrow polydispersity index of 0.24 ± 0.12. The entrapment efficiency of tretinoin was found to be 90.07 ± 4.79%. Clinical studies in healthy human volunteers demonstrated that 90% of the tested individuals had improved skin conditions (reduction in wrinkles), by at least one grade after 4 weeks of treatment. Regarding the development on SLN, it was found that the internal phase concentration did not considerably affect the physicochemical and microbiological properties. Therefore, Hyaluronic acid has potential for the development of SLN applicable to cosmetic formulations, especially for skin. These findings show that the developed SLN have potential for use as cosmetics in the future.

Synthesis of vitamin D3 loaded ethosomes gel to cure chronic immune-mediated inflammatory skin disease: physical characterization, in vitro and ex vivo studies.

The purpose of the current work was to develop and characterize ethosomes of vitamin D3 gel that could more effectively work against psoriasis. Psoriasis is a chronic immune-mediated inflammatory skin disease. Due to vitamin D3 role in proliferation and maturation of keratinocytes, it has become an important local therapeutic option in the treatment of psoriasis. In this research we have initiated worked on ethosomes gels containing vitamin D3 to treat psoriasis. Soya lecithin 1-8% (w/v), propylene glycol and ethanol were used to create the formulations, which were then tested for vesicle size, shape, surface morphology, entrapment effectiveness, and in vitro drug permeation. The drug encapsulation efficiency of ethosomes was 96.25% ± 0.3. The particle sizes of the optimized ethosomes was 148 and 657 nm, and the PDI value was 0.770 ± 0.12 along with negative charge - 14 ± 3. Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) along with thermogravimetric analysis (TGA) studies confirmed the absence of interactions between vitamin D3 and other ingredients. It was determined that the total amount of medication that penetrated the membrane was 95.34% ± 3. Percentage lysis was very negligible for all strengths which were found less than 15%. Based on our research, ethosomes appear to be safe for use. The vitamin D3 ethosomal gel order, description, pH, and viscosity were all within the specified ranges, according to the findings of a 6-month investigation into the stability profile of the completed system. In this research, we successfully prepared ethosomes loaded with vitamin D3 and then converted it into gel for patients' easy applications.

Level of Awareness Regarding Interventional Radiology Among Medical Students at Northern Border University in Arar, Saudi Arabia.

Introduction Interventional radiology (IR) is a highly specialized field of radiology that employs advanced imaging techniques like MRIs, CT scans, X-rays, and ultrasounds to detect and treat a variety of medical disorders. By using minimally invasive procedures, interventional radiologists can access the body's internal organs and tissues with minimal discomfort and reduced risks compared to traditional surgical techniques. Some common IR procedures include angioplasty, embolization, biopsy, and stent placement, among others. Overall, IR is an innovative and effective approach to medical care that offers numerous benefits to patients. As this specialty expands, there is a huge demand for increasing staff. However, due to a lack of awareness, this increased demand could not be fulfilled. Objective The objective is to assess medical students' knowledge regarding IR and compare this knowledge between male and female students. Materials and methods This cross-sectional study was carried out at Northern Border University's College of Medicine in Arar, Saudi Arabia. The study aimed to assess the medical students' knowledge of IR. All students enrolled in the clinical years at Northern Border University were included in the study, and a self-administered online questionnaire was used to collect data. The minimum sample size required was 169. Appropriate statistical analysis was applied to the collected data, and a p-value of less than 0.05 was considered significant. Results One hundred and seventy-two participants in all who met the inclusion criteria answered the study's questionnaire. The fourth-year students represented the highest percentage of the sample, with 65 participants (37.8%), followed by 54 (31.4%) fifth-year students and 53 (30.8%) sixth-year students. The study found that 66 participants (38.4%) rated their knowledge of IR as adequate, while only 8 (4.7%) considered it excellent. The participants' self-rated knowledge of IR did not significantly differ across male and female groups. Conclusion The study's findings suggest that medical students have limited knowledge of IR and that there is no discernible difference in the knowledge and interest of males and females in this subject. Further research and targeted educational interventions may be necessary to improve the medical students' overall knowledge and interest in IR.

Awareness of Radiation Hazards and Knowledge About Radiation Protection Among Medical Students at the Northern Border University, Arar.

Studies have shown that medical students and doctors are not well equipped with knowledge of radiation hazards and their protection. This lack of knowledge may cause harm to patients and healthcare professionals. Objectives To compare the awareness of radiation hazards and knowledge about radiation protection among medical students at Northern Border University, Arar, Saudi Arabia, with and without prior teaching. Methods and materials This cross-sectional study was carried out among medical students from clinical years at Northern Border University, Arar, Saudi Arabia, from May 1st, 2023, to June 30th, 2023. Their consents were taken. Then they were randomly sorted into two groups. One group was given a radiation safety short course, and then they answered a questionnaire. The other group filled out the questionnaire without prior instruction, and analysis was done. The outcome of this study was quantified based on the score calculated after participants filled out the questionnaire. Results The mean score of students who didn't attend the radiology course was 3.38±1.8, while the score of students who attended the radiology course was 7.87±1.4 (p<0.001). Radiology course attendance showed a significant association with knowledge and awareness scores. Conclusions The average knowledge of medical students regarding radiation protection and hazards is quite poor. This lack of understanding could potentially lead to increased risks for both patients and healthcare professionals. The knowledge about radiation hazards and protection is increased in students who attended a short radiology course. We recommend implementing comprehensive educational programs that focus on radiation hazards and protection for medical students.

Unveiling the Genetic Tapestry: Exploring Rhizoctonia solani AG-3 Anastomosis Groups in Potato Crops across Borders.

The current study was carried out to screen 10 isolates (ARS-01-ARS-10) of Rhizoctonia. solani from potato tubers cv. Kuroda, which were collected from various potato fields in Multan, Pakistan. The isolates were found to be morphologically identical, as the hyphae exhibit the production of branches at right angles and acute angles often accompanied by septum near the emerging branches. Anastomosis grouping showed that these isolates belonged to AG-3. A pathogenicity test was performed against the susceptible Kuroda variety and among the isolates, ARS-05 exhibited the highest mean severity score of approximately 5.43, followed by ARS-09, which showed a mean severity score of about 3.67, indicating a moderate level of severity. On the lower end of the severity scale, isolates ARS-06 and ARS-07 displayed mean severity scores of approximately 0.53 and 0.57, respectively, suggesting minimal symptom severity. These mean severity scores offer insights into the varying degrees of symptom expression among the different isolates of R. solani under examination. PCoA indicates that the severe isolate causing black scurf on the Kuroda variety was AG-3. A comprehensive analysis of the distribution, genetic variability, and phylogenetic relationships of R. solani anastomosis groups (AGs) related to potato crops across diverse geographic regions was also performed to examine AG prevalence in various countries. AG-3 was identified as the most widespread group, prevalent in Sweden, China, and the USA. AG-5 showed prominence in Sweden and the USA, while AG-2-1 exhibited prevalence in China and Japan. The phylogenetic analysis unveiled two different clades: Clade I comprising AG-3 and Clade II encompassing AG-2, AG-4, and AG-5, further subdivided into three subclades. Although AGs clustered together regardless of origin, their genetic diversity revealed complex evolutionary patterns. The findings pave the way for region-specific disease management strategies to combat R. solani's impact on potato crops.

Utilization of electronic portal referrals to a community agency for children presenting with an asthma exacerbation to a pediatric emergency department.

PURPOSE: To evaluate referral rates and factors associated with referrals to a community agency for children evaluated for an asthma exacerbation at a pediatric emergency department (PED) and compare PED visits for asthma the following year between those referred and not referred. METHODS: We reviewed electronic health records of children 2-18 years evaluated in our PED from 01/01/2019 to 12/31/2019 with an ICD-10 diagnostic code for asthma (J45x) following the introduction of a portal where clinicians could refer children to a community agency focused on improving health outcomes for asthma. We abstracted data on demographics, PED visits, and hospitalizations and used multivariate logistic regression to evaluate factors associated with referrals. RESULTS: Of the 2262 charts analyzed, the majority of patients were male (61%), Black (76%), and held public insurance (71%). Only a minority of patients (n = 140, 6%) were referred. Age [6-12 years (AOR: 1.93, 95% CI: 1.21-3.08, p = .006), 13-18 years (AOR: 10.61, 95% CI: 6.53-17.24, p = .001)] and lifetime number of PED asthma visits [≥3 visits (AOR: 1.91, 95% CI, 1.01-3.62, p = .05)] were associated with referral. There was no significant difference in the mean number of PED visits in one year [referred: 0.59 (SD1.2) vs. not referred: 0.79 (SD1.3), t = 1.70, p = .09] between the two groups. CONCLUSION: The referral rate to community agency from PED for asthma is low. There was no difference in short-term PED utilization for asthma between those referred and not referred.

Microsponge-Based Gel Loaded with Immunosuppressant as a Simple and Valuable Strategy for Psoriasis Therapy: Determination of Pro-Inflammatory Response through Cytokine IL-2 mRNA Expression.

Tacrolimus (TL) is a topical calcineurin inhibitor immunosuppressive drug widely used to manage various skin disorders. Herein, we report a TL-loaded microsphere gel formulation with severe atopic dermatitis effects that are required to manage skin disorders. The current study adopted a modified emulsion solvent evaporation technique to synthesize TL-loaded microspheres, which were further converted into gels for skin use. Characterization of the synthesized formulation was performed by differential dynamic light scattering, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray crystallography, Brunauer-Emmett-Teller (BET) analysis, differential scanning calorimetry, and drug release. A Franz diffusion cell was used to study the diffusion of TL for up to 8 h at pH 6.8 and 5.5. Evaluation of cell viability was determined by MTT assay and showed higher IC50 values compared to the plain drug. RNA extraction, real-time polymerase chain reaction (RT-PCR), and reverse transcription were also performed to determine the expression levels of the anti-inflammatory cytokine IL-2. Particle size determination was performed by a zeta sizer, and the TL microsphere size was 1745 ± 70 nm with a good polydispersity (0.337 ± 0.12). The drug entrapment efficiency was also very good at 60% ± 10, and the drug release was 93.9% ± 3.5 within 8 h. An in vitro diffusion study of the formulation also showed improved permeability at both pH values (4.5 and 5.5). The findings of the hemolytic tests demonstrated that TL-MG at concentrations of 50, 100, and 200 mg/mL did not produce any hemolysis. A dose-dependent pattern of cytotoxicity was found during the cell viability assay, with an IC50 value of 787.55 ± 12.78 µg/mL. There was a significant decrease in the IL-2 level in the TL-MG group compared to the other groups. TL-MG microspheres were nontoxic carriers for tacrolimus delivery, with greater loading capacity, a significant release profile, and enhanced cellular uptake with improved permeability.

Biopolymer based film loaded with Cholecalciferol: A novel technique to enhance nutritional supplement absorbance.

In terms of delivery systems for active compounds, orally disintegrating films are a great option. The initial stage in creating an oral disintegrating film is selecting a film-forming polymer. The basic polymers combination Microcrystalline Cellulose (MCC), which is co-processed with Carboxymethylcellulose Sodium (CMC) and hydroxypropylmethyl cellulose were used to create an oral disintegrating film that contains cholecalciferol (Vitamin D3), a fat-soluble vitamin that aids in the body's absorption of calcium and phosphorus. The goal of the current inquiry was to develop orally disintegrating films of vitamin D3 to improve patient comfort and compliance for pediatric or elderly patients due to its simplicity of administration. Films containing drugs and made of the appropriate plasticizer and chosen polymers demonstrated outstanding film forming and folding endurance. The dissolution test showed that Vitamin D3 has a rapid disintegration property, with the majority of it dissolving in the medium (pH 6.8) in less than two minutes after being inserted. To verify that the films were successfully formed, a variety of procedures including HPLC, FT-IR and microscopic studies were employed. When kept at 40oC with humidity of 75%, the film showed good stability for at least three months.

Microsponge-derived mini tablets loaded with immunosuppressive agents: Pharmacokinetic investigation in human volunteers, cell viability and IVIVC correlation.

Sirolimus, a potent immunosuppressant, has been demonstrated to have remarkable activity in inhibiting allograft rejection in transplantation. The objective of the study was to fabricate microsponge mini tablets with enhanced solubility and bioavailability. ß-Cyclodextrin and NEOCEL C91 were selected to prepare the microsponges (SLM-M) to improve the stability and solubility of sirolimus. The current study involved the quasi emulsion-solvent diffusion technique to design sirolimus-loaded microsponges that were further compressed into mini tablets 4 mm in diameter. Solid-state characterization, dissolution at different pH values, stability, and pharmacokinetic profiles with IVIVC data were analyzed in humans. Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to characterize the formulations, and high-performance liquid chromatography (HPLC) was used to assess the drug stability of the compressed microsponge minitablets. The API changed from the crystalline state to an amorphous state, as shown by XRD and DSC. The compressed mini tablets showed a 4-fold enhancement in the drug dissolution profile. A toxicology investigation suggested that mini tablets were safe. In humans, the bioavailability of sirolimus compressed mini tablets from SLM-M was significantly improved. The results suggest that mini tablets prepared with ß-cyclodextrin and NEOCEL C91 by a quasi emulsion-solvent diffusion process might be an alternative way to improve the bioavailability of sirolimus. In addition, the manufacturing process is easily scalable for the commercialization of drugs to market.

Novel Hydrolytic Degradable Crosslinked Interpenetrating Polymeric Networks (IPNs): An Efficient Hybrid System to Manage the Controlled Release and Degradation of Misoprostol.

PURPOSE: The goal of this study was to make pH-sensitive HPMC/Neocel C19-based interpenetrating polymeric networks (IPNs) that could be used to treat different diseases. An assembled novel carrier system was demonstrated in this study to achieve multiple functions such as drug protection and self-regulated release. METHODS: Misoprostol (MPT) was incorporated as a model drug in hydroxyl-propyl-methylcellulose (HPMC)- and Neocel C19-based IPNs for controlled release. HPMC- and Neocel C19-based IPNs were fabricated through an aqueous polymerization method by utilizing the polymers HPMC and Neocel C19, the initiator ammonium peroxodisulfate (APS), the crosslinker methylenebisacrylamide (MBA), and the monomer methacrylic acid (MAA). An IPN based on these materials was created using an aqueous polymerization technique. Samples of IPN were analyzed using scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), thermal analysis (TGA), and powder X-ray diffraction (PXRD). The effects of the pH levels 1.2 and 7.4 on these polymeric networks were also studied in vitro and through swelling experiments. We also performed in vivo studies on rabbits using commercial tablets and hydrogels. RESULTS: The thermal stability measured using TGA and DSC for the revised formulation was higher than that of the individual components. Crystallinity was low and amorphousness was high in the polymeric networks, as revealed using powder X-ray diffraction (PXRD). The results from the SEM analysis demonstrated that the surface of the polymeric networks is uneven and porous. Better swelling and in vitro results were achieved at a high pH (7.4), which endorses the pH-responsive characteristics of IPN. Drug release was also increased in 7.4 pH (80% in hours). The pharmacokinetic properties of the drugs showed improvement in our work with hydrogel. The tablet MRT was 13.17 h, which was decreased in the hydrogels, and its AUC was increased from 314.41 ng h/mL to 400.50 ng h/mL in hydrogels. The blood compatibility of the IPN hydrogel was measured using different weights (100 mg, 200 mg, 400 mg, and 600 mg; 5.34%, 12.51%, 20.23%, and 29.37%, respectively). CONCLUSIONS: As a result, IPN composed of HPMC and Neocel C19 was successfully synthesized, and it is now possible to use it for the controlled release of MPT.

Control synthesis of mesoporous silica microparticles: Optimization and in vitro cytotoxicity studies.

The current paper explains how to make mesoporous silica microparticles (MSM) by mixing water and dichloromethane. Several dichloromethane-water ratios were used to adjust the reaction mixture for the first time to easily synthesize mesoporous silica micro particles with regulated particle size. By carefully modifying the concentrations of water and dichloromethane, a higher level of consistency was achieved in the production of micro particles, i.e. to a 2:1 v/v ratio. It was discovered that variations in the dichloromethane-to-water ratios significantly affect the surface roughness and morphologies of mesoporous silica particles along with size. This is most likely because the solvent affects how quickly tetraethyl orthosilicate (TEOS) and how quickly inorganic species polymerize. In all experiments, conditions were maintained the same at 25oC temperature and 1000 rpm. Scanner electron microscopy (SEM), Fourier transform infrared (FTIR) and X-ray powder diffraction (XRD) methods were used to identify the structure of MSM. The in vitro cytotoxicity assays showed that the produced particles, which had a diameter of 1.0 m, were safe for usage in the cellular system.

RP-HPLC method to assay ethinylestradiol and drospirenone with 3D chromatograph model in fixed dose in rat plasma for pharmacokinetic study analysis.

For the simultaneous measurement of Ethinylestradiol (EE) and Drospirenone (DP) in fixed-dose combination hormones tablets, a reverse-phase high-performance liquid chromatographic (RP-HPLC) method was developed. A specific, precise and accurate RP-HPLC method was developed and validated to analyse the drugs in rat plasma. The fluorescence detection for EE was made at λ= 200-310 nm and Ultraviolet-visible (UV/Vis) detection for DP was made at 270 nm. The typical EE and DP retention times were 4.19 and 5.30 minutes, respectively. The limit of detection (LOD) and limit of detection (LOQ) for EE were 0.121 and 0.282µg/mL and LOD and LOQ for DP were 2.23 and 7.697µg/mL respectively. The regression coefficient (r2) of EE and DP were 0.9937 and 0.9913 respectively. Precision's relative standard deviation (RSD) was less than 5%. The analyte recoveries of both drugs stayed within 95% of each other. All other validation parameters adhered to ICH standards. Throughout the analytical process, the analyte was stable. The advantages of the method developed include stability under different conditions and a low limit of quantification that was in micrograms. Its applicability was confirmed by the analysis of EE and DP levels in plasma samples in a designed pharmacokinetic study in rats after oral administration.

Amikacin-Loaded Chitosan Hydrogel Film Cross-Linked with Folic Acid for Wound Healing Application.

PURPOSE: Numerous carbohydrate polymers are frequently used in wound-dressing films because they are highly effective materials for promoting successful wound healing. In this study, we prepared amikacin (AM)-containing hydrogel films through the cross-linking of chitosan (CS) with folic acid along with methacrylic acid (MA), ammonium peroxodisulfate (APS), and methylenebisacrylamide (MBA). In the current studies, an effort has been made to look at the possibilities of these materials in developing new hydrogel film wound dressings meant for a slow release of the antibiotic AM and to enhance the potential for wound healing. METHODS: Free-radical polymerization was used to generate the hydrogel film, and different concentrations of the CS polymer were used. Measurements were taken of the film thickness, weight fluctuation, folding resistance, moisture content, and moisture uptake. HPLC, FTIR, SEM, DSC, and AFM analyses were some of the different techniques used to confirm that the films were successfully developed. RESULTS: The AM release profile demonstrated regulated release over a period of 24 h in simulated wound media at pH 5.5 and 7.4, with a low initial burst release. The antibacterial activity against gram-negative bacterial strains exhibited substantial effectiveness, with inhibitory zones measuring approximately 20.5 ± 0.1 mm. Additionally, in vitro cytocompatibility assessments demonstrated remarkable cell viability, surpassing 80%, specifically when evaluated against human skin fibroblast (HFF-1) cells. CONCLUSIONS: The exciting findings of this study indicate the promising potential for further development and testing of these hydrogel films, offering effective and controlled antibiotic release to enhance the process of wound healing.

Developing Nanosuspension Loaded with Azelastine for Potential Nasal Drug Delivery: Determination of Proinflammatory Interleukin IL-4 mRNA Expression and Industrial Scale-Up Strategy.

In order to increase bioavailability and intranasal absorbance, the current work set out to create azelastine nasal spray based on nanosuspension. Chondroitin was utilized as a polymer to prepare azelastine nanosuspension through the precipitation procedure. A size of 500 nm and a polydispersity index of 0.276 with a negative potential (-20 mV) were achieved. X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, thermal analysis including differential scanning calorimetry and thermogravimetric analysis, in vitro release, and diffusion studies were used to characterize the optimized nanosuspension. MTT assay was used to assess the viability of the cells, and hemolysis assay was used to assess the blood compatibility. Using RNA extraction and reverse transcription polymerase chain reaction, the levels of the anti-inflammatory cytokine IL-4, which is most closely related to cytokines in allergic rhinitis, were measured in mouse lungs. The drug dissolution and diffusion study indicated 2.0-fold increase compared to pure reference sample. Therefore, the azelastine nanosuspension could be suggested as a practical and simple nanosystem for intranasal delivery with improved permeability and bioavailability. The outcome obtained in this study indicated that azelastine nanosuspension has great potential to treat allergic rhinitis as intranasal treatment.

Formulation and Characterization of Polymeric Cross-Linked Hydrogel Patches for Topical Delivery of Antibiotic for Healing Wound Infections.

Wound healing faces significant challenges in clinical settings. It often contains a series of dynamic and complex physiological healing processes. Instead of creams, ointments and solutions, alternative treatment approaches are needed. The main objective of the study was to formulate bacitracin zinc-loaded topical patches as a new therapeutic agent for potential wound healing. A free radical polymerization technique was optimized for synthesis. Polyethylene glycol-8000 (PEG-8000) was chemically cross-linked with acrylic acid in aqueous medium, using Carbopol 934 as a permeation enhancer and tween 80 as surfactant. Ammonium persulfate and N,N'-Methylenebisacrylamide (MBA) were utilized as initiator and cross-linker. FTIR, DSC, TGA, and SEM were performed, and patches were evaluated for swelling dynamics, sol-gel analysis, in vitro drug release in various media. A Franz diffusion cell was used for the permeation study. Irritation and wound healing with the drug-loaded patches were also studied. The characterization studies confirmed the formation of a cross-linked hydrogel network. The highest swelling and drug release were observed in formulations containing highest Polyethylene glycol-8000 and lowest N,N'-Methylenebisacrylamide concentrations. The pH-sensitive behavior of patches was also confirmed as more swelling, drug release and drug permeation across skin were observed at pH 7.4. Fabricated patches showed no sign of irritation or erythema as evaluated by the Draize scale. Faster wound healing was also observed with fabricated patches compared to marketed formulations. Therefore, such a polymeric network can be a promising technology for speeding up wound healing and minor skin injuries through enhanced drug deposition.

Population Genetics and Anastomosis Group's Geographical Distribution of Rhizoctonia solani Associated with Soybean.

Rhizoctonia solani is a species complex composed of many genetically diverse anastomosis groups (AG) and their subgroups. It causes economically important diseases of soybean worldwide. However, the global genetic diversity and distribution of R. solani AG associated with soybean are unknown to date. In this study, the global genetic diversity and distribution of AG associated with soybean were investigated based on rDNA-ITS sequences deposited in GenBank and published literature. The most prevalent AG, was AG-1 (40%), followed by AG-2 (19.13%), AG-4 (11.30%), AG-7 (10.43%), AG-11 (8.70%), AG-3 (5.22%) and AG-5 (3.48%). Most of the AG were reported from the USA and Brazil. Sequence analysis of internal transcribed spacers of ribosomal DNA separated AG associated with soybean into two distinct clades. Clade I corresponded to distinct subclades containing AG-2, AG-3, AG-5, AG-7 and AG-11. Clade II corresponded to subclades of AG-1 subgroups. Furthermore, AG and/or AG subgroups were in close proximity without corresponding to their geographical origin. Moreover, AG or AG subgroups within clade or subclades shared higher percentages of sequence similarities. The principal coordinate analysis also supported the phylogenetic and genetic diversity analyses. In conclusion, AG-1, AG-2, and AG-4 were the most prevalent AG in soybean. The clade or subclades corresponded to AG or AG subgroups and did not correspond to the AG's geographical origin. The information on global genetic diversity and distribution will be helpful if novel management measures are to be developed against soybean diseases caused by R. solani.

Developing of SiO2 Nanoshells Loaded with Fluticasone Propionate for Potential Nasal Drug Delivery: Determination of Pro-Inflammatory Cytokines through mRNA Expression.

Mesoporous Silica Nanoparticles (MSN) are porous inorganic materials that have been extensively used for drug delivery due to their special qualities, such as biocompatibility, biodegradability, and non-toxicity. MSN is a promising drug delivery system to enhance the efficacy and safety of drug administration in nasal diseases like chronic rhinitis (CR). In this study, we used the sol-gel technique for MSN synthesis and incorporate fluticasone propionate (FP) for intranasal drug administration for the treatment of chronic rhinitis (CR). In order to confirm the particle size, shape, drug release, and compatibility, various instruments were used. MSN was effectively prepared with average sizes ranging between 400 ± 34 nm (mean ± SD) as measured by dynamic light scattering (DLS), while zeta potential verified in all cases their positive charged surface. To investigate MSN features, the Fourier transform infrared spectrometer (FTIR), scanning electron microscopy (SEM), transmission electron microscope (TEM), thermal analysis, X-ray diffraction (XRD), and nitrogen adsorption/desorption measurement were used. The loaded compound was submitted to in vitro dissolution tests, and a remarkable dissolution rate improvement was observed compared to the crystalline drug in both pH conditions (1.2 and 7.4 pH). By using an MTT assay cell viability was assessed. The expression levels of the anti-inflammatory cytokines IL-4 and IL-5 were also measured using mRNA extraction from rat blood. Other characterizations like acute toxicity and hemolytic activity were also performed to confirm loaded MSN safety. Loaded MSN was incorporated in nasal spray prepared by using innovator excipients including poloxamer. After this, its nasal spray's physical characteristics were also determined and compared with a commercial product (Ticovate).

Fabrication of pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 for the controlled release of ketorolac: its characterization and acute oral toxicity study.

OBJECTIVE: Ketorolac tromethamine (KT), selected as a model drug, is used in management of moderate to severe acute pain. It has a short half-life (∼5.5 h) and requires frequent dose administration when needed for longer period of time. In our current project, we designed pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 (CS/Pl) for the controlled release of ketorolac. METHODS: Hydrogel blends were fabricated using free radical polymerization reaction technique utilizing different ratios of chondroitin sulfate (CS) (polymer) and pluronic F-127 (polymer), acrylic acid (monomer), N,N'-methyl-bisacrylamide (MBA) (cross-linker), initiator ammonium persulfate (APS) and tween-80 (surfactant). The fabricated hydrogel blends were studied and evaluated for pH responsiveness, swelling, water absorbency, in vitro drug release, and morphological characteristics such as SEM, XRD, FTIR, and TGA/DSC. Acute toxicity study was performed on rabbits. RESULTS: Maximum swelling and water absorbency were shown by CS/Pl blends being significantly greater at 7.4 (basic pH) than in 1.2 (acidic pH). In vitro dissolution demonstrated pH responsive controlled KT release following zero order at higher pH (7.4) medium up to 36 h. FTIR studies confirmed the structures of our blends; SEM results showed porous framework; thermal studies revealed higher stability of hydrogels than the individual polymers; and XRD confirmed the nature of our blends. Toxicity study revealed the nontoxic nature of the hydrogel blends. CONCLUSION: The prepared CS/Pl hydrogels demonstrated stimuli-controlled release with delivery of drug for prolonged period of time and thus can minimize dosing frequency, safe drug delivery, increased patient compliance and easiness.