Effect of quercetin-loaded poly (lactic-co-glycolic) acid nanoparticles on lipopolysaccharide-induced memory decline, oxidative stress, amyloidogenesis, neurotransmission, and Nrf2/HO-1 expression.

Neuroinflammation contributes to the pathogenesis of several neurodegenerative disorders. This study examined the neuroprotective effect of quercetin (QUR)-loaded poly (lactic-co-glycolic) acid (PLGA) nanoparticles (QUR NANO) against the neurotoxicity induced by lipopolysaccharide (LPS) in mice. A QUR NANO formulation was prepared and characterized by differential scanning calorimetry, X-ray diffraction, entrapment efficiency (EE), high-resolution transmission electron microscopy, field emission scanning electron microscopy, and in vitro drug release profile. Levels of glutathione, malondialdehyde, catalase, inducible nitric oxide synthase (iNOS), amyloid beta 42 (Aß42), ß-secretase, gamma-aminobutyric acid (GABA), and acetylcholine esterase (AChE) were measured in the mouse brain tissues. The gene expression of nuclear factor erythroid-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1) were also determined. The prepared QUR NANO formulation showed 92.07 ± 3.21% EE and drug loading of 4.62 ± 0.55. It exhibited clusters of nano-spherical particles with smooth surface areas, and the loading process was confirmed. In vivo, the QUR NANO preserved the spatial memory of mice and protected the hippocampus from LPS-induced histological lesions. The QUR NANO significantly reduced the levels of malondialdehyde, iNOS, Aß42, ß-secretase, and AChE in brain tissue homogenates. Conversely, QUR NANO increased the glutathione, catalase, and GABA concentrations and upregulated the expression of Nrf-2 and HO-1 genes. Remarkably, the neuroprotective effect of QUR NANO was significantly greater than that of herbal QUR. In summary, the prepared QUR NANO formulation was efficient in mitigating LPS-induced neurotoxicity by reducing memory loss, oxidative stress, and amyloidogenesis while preserving neurotransmission and upregulating the expression of Nrf2 and HO-1 genes. This study addresses several key factors in neuroinflammatory disorders and explores the potential of QUR-loaded nanoparticles as a novel therapeutic approach to alleviate these factors.

Naringin-Dextrin Nanocomposite Abates Diethylnitrosamine/Acetylaminofluorene-Induced Lung Carcinogenesis by Modulating Oxidative Stress, Inflammation, Apoptosis, and Cell Proliferation.

Nanotechnology has proven advantageous in numerous scientific applications, one being to enhance the delivery of chemotherapeutic agents. This present study aims to evaluate the mechanisms underlying the chemopreventive action of naringin-dextrin nanocomposites (Nar-Dx-NCs) against diethylnitrosamine (DEN)/2-acetylaminofluorene (2AAF)-induced lung carcinogenesis in male Wistar rats. DEN was administered intraperitoneally (i.p.) (150 mg/kg/week) for two weeks, followed by the oral administration of 2AAF (20 mg/kg) four times a week for three weeks. Rats receiving DEN/2AAF were concurrently treated with naringin or Nar-Dx-NCs orally at a dose of 10 mg/kg every other day for 24 weeks. Naringin and Nar-Dx-NCs treatments prevented the formation of tumorigenic cells within the alveoli of rats exposed to DEN/2AAF. These findings were associated with a significant decrease in lipid peroxidation, upregulation of antioxidant enzyme (glutathione peroxidase and superoxide dismutase) activity, and enhanced glutathione and nuclear factor erythroid 2-related factor 2 expression in the lungs. Naringin and Nar-Dx-NCs exerted anti-inflammatory actions manifested by a decrease in lung protein expression of tumor necrosis factor-α and interleukin-1ß and mRNA expression of interleukin-6, interferon-γ, nuclear factor-κB, and inducible nitric oxide synthase, with a concurrent increase in interleukin-10 expression. The anti-inflammatory effect of Nar-Dx-NCs was more potent than naringin. Regarding the effect on apoptosis, both naringin and Nar-Dx-NCs significantly reduced Bcl-2 and increased Bax and P53 expressions. Moreover, naringin or Nar-Dx-NCs induced a significant decrease in the expression of the proliferator marker, Ki-67, and the effect of Nar-Dx-NCs was more marked. In conclusion, Nar-Dx-NCs improved naringin's preventive action against DEN/2AAF-induced lung cancer and exerted anticarcinogenic effects by suppressing oxidative stress and inflammation and improving apoptotic signal induction and propagation.

Protective Effects of Naringin-Dextrin Nanoformula against Chemically Induced Hepatocellular Carcinoma in Wistar Rats: Roles of Oxidative Stress, Inflammation, Cell Apoptosis, and Proliferation.

Nanotechnology holds great promise for the development of treatments for deadly human diseases, such as hepatocellular carcinoma (HCC). In the current study, we compared the hepatoprotective effects of naringin-dextrin nanoparticles (NDNPs) against HCC in male Wistar rats with those of pure naringin and investigated the underlying cellular and molecular mechanisms. HCC was induced by intraperitoneal injection of diethylnitrosamine (DEN, 150 mg/kg body weight (b.w.) per week) for two weeks, followed by oral administration of 2-acetylaminofluorene (2AAF, 20 mg/kg b.w.) four times per week for three weeks. DEN/2AAF-administered rats were divided into three groups that respectively received 1% carboxymethyl cellulose (as vehicle), 10 mg/kg b.w. naringin, or 10 mg/kg b.w. NDNP every other day by oral gavage for 24 weeks. Both naringin and NDNP significantly attenuated the harmful effects of DEN on liver function. Both compounds also suppressed tumorigenesis as indicated by the reduced serum concentrations of liver tumor markers, and this antitumor effect was confirmed by histopathological evaluation. Additionally, naringin and NDNP prevented DEN-induced changes in hepatic oxidative stress and antioxidant activities. In addition, naringin and NDNP suppressed inflammation induced by DEN. Moreover, naringin and NDNP significantly reduced the hepatic expression of Bcl-2 and increased Bax, p53, and PDCD5 expressions. Naringin and NDNP also reduced expression of IQGAP1, IQGAP3, Ras signaling, and Ki-67 while increasing expression of IQGAP2. Notably, NDNP more effectively mitigated oxidative stress and inflammatory signaling than free naringin and demonstrated improved antitumor efficacy, suggesting that this nanoformulation improves bioavailability within nascent tumor sites.

Novel Cold Cure Acrylic Denture Base with Recycled Zirconia Nano-Fillers That Were Functionalized by HEMA Agent Incorporation: Using the Sprinkle Approach.

Background: Though acrylic resins possess many useful properties, denture fracture is nevertheless a familiar issue. Objective: This study aimed to determine the effect of low-percent recycled Zirconia nanoparticles as filler on the transverse strength, impact strength, surface hardness, water sorption, and solubility of resin using the sprinkle cold-curing technique. Materials and Methods: Various formulae were prepared and mixed with PMMA (polymer) powder containing varying percentages (0.01%, 0.1%, 0.3%, and 0.5%) of recycled ZrO2NPs to mono-methyl methacrylate (MMA monomer). A 2-hydroxyethyl-methacrylate (HEMA) agent was used to functionalize recycled zirconia (ZrO2) nano-fillers. X-ray diffraction, field emission scanning electron microscopy, high-resolution transmission electron microscopy, energy-dispersive X-ray spectroscopy, and dynamic light scattering were used to characterize the samples. For mechanical tests, standard metallic moulds (according to American Dental Association specification no. 27) were machined for 60 specimens' preparation, 12 for each percent (zero, 0.01%, 0.1%, 0.3%, and 0.5%). A one-way ANOVA test was used to compare the five groups for parametric data, while the Kruskal-Wallis test was employed for nonparametric data. The P 0.05 value was accepted as the significance level. All formulae were tested for cytotoxicity at 24 and 48 hours on WI38 normal lung cell lines. Results: The XRD analysis demonstrated the tetragonal crystallographic structure of the recycled zirconia nanoparticles. Incorporating a low percentage of recycled ZrO2 nanoparticles (0.01%, 0.1%, 0.3%, and 0.5%) improved the tested properties of PMMA to different degrees in a significant and non-significant pattern, while the optimal tested percent was 0.3%. Conclusion: The 0.3% percentage of recycled zirconia nanoparticles maintained and improved the physical and mechanical properties of acrylic resin. Recycled ZrO2/PMMA nanocomposite is a synergistic candidate due to its economic return and clinical application safety.

Therapeutic significance of thymoquinone-loaded chitosan nanoparticles on streptozotocin/nicotinamide-induced diabetic rats: In vitro and in vivo functional analysis.

To overcome the low bioavailability of lipophilic free thymoquinone (TQ), this study aims to evaluate a novel oral formula of TQ-loaded chitosan nanoparticles (TQ-CsNPs) for the effective treatment of diabetes. The XRD, FTIR, FESEM, HRTEM, and dynamic light scattering were all conducted on the prepared formula. The release pattern of TQ, cytotoxicity against MRC-5 cell line (human lung fibroblast cells), and antidiabetic activity on streptozotocin/nicotinamide (STZ/NA) rat model of diabetes were investigated. The results confirmed the formation of TQ-CsNPs with an entrapment efficiency of 75.7 ± 6.52 %, a mean Zetasizer distribution of 84.25 nm, and an average particle size of about 50 nm. After 24 h, the percentage of free TQ-cumulative release was approximately 35.8 %, whereas TQ-CsNPs showed a sustained release pattern of 78.5 %. The investigated formula was not toxic to normal lung cells, and more efficient in ameliorating the altered glycemia, dyslipidemia, inflammation, and oxidative stress induced by STZ/NA than free TQ, blank CsNPs, and metformin-HCl (as a reference drug). Additionally, TQ-CsNPs restored the normal pancreatic islets' configuration and morphometry, suggesting a potent insulinotropic action. In conclusion, the antidiabetic efficacy of TQ was improved by engaging TQ with CsNPs as an excellent nanoplatform to enhance the oral bioavailability of TQ.

Theranostics platform of Abemaciclib using magnetite@silica@chitosan nanocomposite.

The current study was designed to synthesize a nanoformula comprising of magnetite nanoparticles (MN) with mesoporous silica (MS), which was in turn coated with chitosan (CS) and further loaded with a chemotherapeutic agent, Abemaciclib (ABE). The prepared formula, MN@MS@CS@ABE, was characterized by XRD, FTIR, HRTEM, FESEM, DLS, VSM, BET, and BJH. The ABE loading capacity and entrapment efficiency were calculated, and an in vitro drug release experiment was conducted. Cytoxicity was studied by the MTT assay. The formula was investigated as an anticancer agent versus MCF-7 cells by performing Annexin V-FITC flow cytometry and cell cycle analysis. Furthermore, we examine the formula as a contrast agent in magnetic resonance imaging (MRI). ABE loading and encapsulation efficiency were 24.2 % and 63.4 %, respectively. The formula demonstrated sustained drug release behavior for 72 h. The MTT assay revealed a higher cytotoxicity of free ABE in MCF-7 cells compared to MN@MS@CS@ABE. Flow cytometry revealed early and late phases of apoptosis and necrosis with different percentages. The formula stimulated a reduction in signal intensity in the MR T2-weighted imaging technique. In conclusion, the current study developed a nanoformula which could be a promising theranostic agent in cancer therapy and diagnosis.

A novel layered double hydroxide-hesperidin nanoparticles exert antidiabetic, antioxidant and anti-inflammatory effects in rats with diabetes.

BACKGROUND: Incidence of diabetes has increased significantly worldwide over recent decades. Our objective was to prepare and characterize a novel nano-carrier of hesperidin to achieve a sustained release of hesperidin and to explore the potency of the novel formula as an antidiabetic agent compared to metformin in type 2 diabetic rats. METHODS: Hesperidin was loaded on MgAl-layered double hydroxide (LDH). The formula was characterized using Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), transmission electron microscopy, and dynamic light scattering. The release profile of hesperidin and MgAl-LDH-Hesperidin were studied in vitro. The parameters studied in vivo were blood glucose, glycated hemoglobin (HbA1c), insulin, lipid profile, and liver glycogen levels. We also investigated the levels of interleukin (IL)-17, tumor necrosis factor-Alfa (TNF-α), malondialdehyde (MDA), catalase, and the mRNA expression of peroxisome proliferator-activated receptor-gamma (PPARγ) and nuclear factor erythroid 2-related factor-2 (NrF2). RESULTS: There were variations in the XRD patterns and FTIR confirming the physical adsorption of hesperidin on the surface of LDH. The results indicated that the diabetic rats treated with administration of antidiabetic formula, MgAl-LDH-Hesperidin, showed a beneficial effect on the levels of blood glucose, insulin, HbA1c%, and lipid profile, comparing to diabetic control rats. The antidiabetic agent also showed a significant decrease in the levels of TNF-α, IL-17, and MDA, and an increase in the level of catalase. Marked upregulation of the expression levels of mRNA for PPARγ and NrF2 were recorded. CONCLUSION: The novel nano-hesperidin formula MgAl-LDH-Hesperidin revealed a sustained release of hesperidin and exhibited antidiabetic, antihyperlipidemic, antioxidant, and anti-inflammatory properties, and also is a promising agent for effective delivery of drugs to treat type 2 diabetes.

Hepatoprotective Effects of Polydatin-Loaded Chitosan Nanoparticles in Diabetic Rats: Modulation of Glucose Metabolism, Oxidative Stress, and Inflammation Biomarkers.

Polydatin (PD) has a broad range of pharmacological activities; however, its effects on diabetic liver damage are poorly studies. This work is aimed to explore possible protective effects of polydatin-loaded chitosan nanoparticles (PD-CSNPs) or PD against liver damage associated with diabetes. Diabetes was induced in rats using nicotinamide/streptozotocin treatment. Diabetic rats were then divided into six groups: normal control rats, diabetic control rats, and rats orally treated with PD, PD-CSNPs, equivalent unloaded CSNPs, or metformin daily for 4 weeks. Treatment with PD and PD-CSNPs significantly reduced the blood glucose content, lipid peroxidation in the liver, and activities of serum transaminases and carbohydrate metabolism enzymes (including succinate dehydrogenase and pyruvate kinase); by contrast, liver glycogen content, glutathione concentration, and activities of the antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase, and glucose-6-phosphate dehydrogenase) were markedly increased compared with the control diabetic rats. Furthermore, expression of the tumor necrosis factor α and interleukin-1ß mRNAs was significantly downregulated, while expression of glucose transporter 2 and glucokinase mRNAs was strongly upregulated vs. control diabetic rats. We concluded that PD-CSNPs and PD ameliorate diabetic liver damage by modulating glucose transporter 2 expression, affecting the activity of carbohydrate metabolism enzymes, and suppressing oxidative stress and inflammation, PD-CSNPs being more efficient than PD, probably due to higher bioavailability and prolonged release.

A Highly Cellular Uptake Ternary Nanocomposite Titanate Nano-Tubes/CuFe2O4/Zn-Fe Could Induce Intrinsic Apoptosis of Prostate Cancer Cells: An Extended Study.

Our previously prepared ternary nanocomposite TNT/CuFe2O4/Zn-Fe was highly engulfed by PC-3 cells, activated cytotoxicity that was dosage and time-subordinated, and demonstrated morphological alteration, which is one of the common characteristics of apoptotic cells. This prolonged study aimed to investigate other items. The study performed assays as Annexin V-FITC, flow cytometry, DNA ladder electrophoresis, and ROS assay for apoptosis detection, cell cycle analysis, DNA fragmentation, and ROS generation, respectively. In the PC-3-treated cells, the early and late phases of apoptosis with different percentages and DNA fragmentation were determined. Besides, the PC-3 cell cycle revealed the three major cell distribution different phases of the cycle (G1, S, and G2/M), and the Sub G1, which corresponded to apoptotic cells. The results proved the presence of ROS that triggered the intrinsic apoptotic pathway, which was confirmed through a decrease in (Bcl-2), the release of cytochrome c, activation of caspase-9, and caspase-3. To conclude, the ternary nanocomposite TNT/CuFe2O4/Zn-Fe achieved biochemical features alterations and could induce intrinsic apoptosis of PC-3 cells. The planned work of the current research will illuminate the arrested phase in the cell cycle through studying tumor suppressor genes such as p53 and Retinoblastoma RB, c-Myc oncogene, and cyclin-dependent kinases (Cdks) as well as their regulators.

An Herbal Nanohybrid Formula of Epigallocatechin Gallate-Chitosan-Alginate Efficiently Restrict the Sexual Dysfunction Adverse Effect of ß-Adrenergic Antagonist Drug: Propranolol.

The clinical studies proved the adverse effect of Propranolol on sexual function. Regarding this issue, the key research question of this study was, whether the designed herbal nanohybrid formula EGCG-chitosan-alginate has an efficacy versus Propranolol, or not? The formula was optimized according to the coacervation method. Its molecular structure and characteristics were confirmed. The entrapment efficiency was determined, and the stability, as well in vitro release study was conducted. The in vivo study was conducted for 65 days. To answer the raised question, tissue weights of the testis, epididymis seminal vesicles, and prostate were determined. Oxidative stress markers as MDA and GSH were measured in testis and epididymis, while testosterone in blood serum. The semen analysis was performed. DNA damage was detected according to the comet assay procedures. Conventional pathological examination was done in special concern to testis and epididymis. The characterization results reflected the good preparation of the formula with an amorphous structure in a range of 200 nm, high stability with ZP + 57.3 mV. The calculated EE was 84.10 ± 1.19% and the release percent was 72.11 ± 0.77% for 24 hrs. All the rats increased in the weight with variations among the groups in the tissue organs. The finding exposed a significant decrease in the average of MDA in the rats' testes with a significant increase in GSH while a non-significant difference in the epididymis, in both. The testosterone, the seminal parameters, and the DNA integrity significantly increased in the nano-formula compared to propranolol. Likewise, normal pathological findings of the nano-formula in the testis and Epididymis compared to abnormal of propranolol. In total, the current research confirmed that EGCG had no toxic effects and able to promote fertility. The most important finding was the administration of EGCG either in normal or nano-form prior to propranolol alleviated the effects of propranolol. These findings reflected the protection evident of EGCG versus propranolol.

Chemisorption and sustained release of cefotaxime between a layered double hydroxide and polyvinyl alcohol nanofibers for enhanced efficacy against second degree burn wound infection.

Zn-Al layered double hydroxides (LDHs) were synthesized by a chemical method, while polyvinyl alcohol (PVA) nanofibers were fabricated by an electrospinning approach; we also synthesized Zn-Al LDH/cefotaxime (cefotax), Zn-Al LDH@PVA, and Zn-Al LDH/cefotax@PVA (LCP). Characterizations were performed by X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, high-resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, Brunauer-Emmett-Teller analysis, thermogravimetric-differential thermal analysis techniques, dynamic light scattering, X ray-florescence, and carbon, hydrogen, and nitrogen (CHN) analyses. The adsorption isotherm of cefotax and its entrapment percentage, release, and kinetics were also investigated. The results confirmed the elemental constituents of the mentioned formulas, which exhibited different degrees of crystallinity and different morphologies. Besides, these formulas were tested in vitro as antimicrobial agents and applied in vivo against second-degree wound burns induced in rats' skin. The adsorption of cefotax occurred chemically, and the experimental data were fitted with different isotherm models, where the Freundlich and Toth models gave the best fits. The entrapment percentage in LDH/cefotax was 77.41% and in LDH/cefotax@PVA, it was 67.83%. The sustained release of cefotax from LDH and LCP was attainable; the release percentages were 89.31% and 81.55% in up to 12 h, respectively. The release kinetics of cefotax from LDH fitted well with first-order kinetics, while that for LCP was parabolic. The formulas showed uneven antimicrobial effects against Gram-positive and Gram-negative bacteria; the best effect was exhibited by Zn-Al LDH/cefotax@PVA due to its sustained release. Finally, investigating the possibility of using these formulas in the clinical setting should be considered.

Synthesis and evaluation of layered double hydroxide/doxycycline and cobalt ferrite/chitosan nanohybrid efficacy on gram positive and gram negative bacteria.

The current study tested the antibacterial activity of layered double hydroxide (LDH), LDH-Doxycycline nanohybrid, Cobalt ferrite nanoparticles (NPs) and Cobalt ferrite-Chitosan nanohybrid against Gram-negative bacteria Escherichia coli. In addition, the study investigated the Cobalt ferrite NPs and Cobalt ferrite-Chitosan nanohybrids against Gram-positive bacteria Staphylococcus aureus. The nanoparticles and nanohybrids were synthesized by a chemical method and characterized by high resolution transmission electron microscope (HRTEM), X-ray diffraction (XRD), and Fourier transformation Infra-red Spectroscopy (FTIR). Multi-point Brunauer-Emmet-Teller (BET) method determined the specific surface area while Barrett-Joyner-Halenda for (BJH) figured the corresponding specific pore volume and pore size and Zetasizer ranked the particle size distribution. Minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) measurements besides agar well diffusion method showed the antimicrobial activity of the nanoparticles. The results revealed no antibacterial activity of the LDH and Cobalt ferrite NPs alone. Meanwhile, the Cobalt ferrite-Chitosan nanohybrid and LDH-Doxycycline showed a high activity antibacterial effect.