Fabrication of ibuprofen/naringenin-coloaded into zein/sodium caseinate nanoparticles: evaluation of antiproliferative activity and apoptosis induction in liver cancer cells.

Nowadays, liver cancer is one of the most disturbing types of cancer that can affect either sex. Nanoparticles (NPs) of zein/sodium caseinate incorporating ibuprofen (IBU) and naringenin (NAR) have improved bioavailability and a high encapsulation efficiency (EE%). These nanoparticles are uniformly spherical. In vitro, cytotoxicity analysis on HepG2 cell lines, which are used to study human liver cancer, shows that encapsulated drugs (86.49% ± 1.90, and 78.52% ± 1.98 for NAR and IBU, respectively) have significantly lower IC50 values than individual drugs or their combined free form. In addition, the combination indices of 0.623 and 0.155 for IBU and NAR, respectively, show that the two have joint beneficial effects. The scratch wound healing assay results also show that the free drugs and the engineered NPs have a more significant anti-migratory effect than the untreated cells. The designed nanoparticles also reduce angiogenesis and proliferation while inducing apoptosis, according to in vitro results. In conclusion, a new approach to treating liver cancer may lie in the nanoencapsulation of numerous drugs within nanoparticles.

Cu-W bimetallic nanoparticles decorated g-C3N4 sheets: Facile construction and characterization for perception of dopamine in sensing application.

In this study, we present the development and analysis of electrochemical sensors utilizing graphitic carbon nitride copper-tungsten nanoparticles (g-C3N4 @Cu-W Nps) capped with various cationic surfactants of differing chain lengths and counter ions. The fabricated nanoparticles underwent thorough characterization to assess their morphological, structural, and compositional attributes, revealing their uniformity, spherical morphology, and monoclinic crystal phases. Subsequently, these nanoparticles were employed in the fabrication of electrochemical sensors for hydrazine detection. A comprehensive comparison of the electrochemical responses, evaluated via cyclic voltammetry, was conducted between sensors utilizing bare nanoparticles and those capped with surfactants.

Biofabrication of bimetallic selenium@zinc nanoparticles using Champia parvula aqueous extract: Investigation of anticancer activity and its apoptosis induction.

Selenium@zinc nanoparticles, or Se@Zn NPs, are extensively employed in various environmental, industrial and biological domains. However, the biological potential of Se@Zn NPs has not been thoroughly investigated. This study focused on fabricating Se@Zn NPs from algae using an aqueous extract of Champia parvula seaweed. Analytical techniques were used to describe the successfully synthesized Se@Zn NPs. In addition, a biological function analysis of the Se@Zn NPs was conducted. The Ultraviolet-visible spectroscopy (UV-vis) spectrum showed a specific absorbance peak for the Se@Zn NPs at 350-400 nm. The biomolecules involved in forming Se@Zn NPs were identified by their potential functional groups, as revealed by Fourier transform infrared spectroscopy (FTIR). By scanning electron microscopy (SEM) and transmission electron microscopy (TEM), Se@Zn NPs were shown to be spherical and to have a diameter range of 100-200 nm. NPs with a crystallite diameter of 54.8 nm and chemical compositions of zinc and selenium (1:1.5 ratio) were revealed by X-ray diffraction analysis (XRD) and energy dispersive x-ray spectroscopy (EDS). IC50 values were determined for the anticancer activity against A549, MCF-7 and HeLa cells. Cell morphological changes in fluorescence microscopy and apoptosis mechanisms by flow cytometry analysis were investigated, which show that Se@Zn NPs induced apoptosis in various cancer cells. DNA fragmentation and ROS levels were studied by fluorescence microscopy. In conclusion, conditions required for therapeutic and preventative applications may be met by the green synthesis of Se@Zn NPs.

Investigation of antiproliferative efficacy and apoptosis induction in leukemia cancer cells using irinotecan-loaded liposome-embedded nanofibers constructed from chitosan.

Liposomes and nanofibers have been implemented as efficacious vehicles for delivering anticancer drugs. With this view, this study explores the antiproliferative efficacy and apoptosis induction in leukemia cancer cells utilizing irinotecan-loaded liposome-embedded nanofibers fabricated from chitosan, a biological source. Specifically, we investigate the effectiveness of poly(ε-caprolactone) (PCL)/chitosan (CS) (core)/irinotecan (CPT)nanofibers (termed PCL-CS10 CPT), PCL/chitosan/irinotecan (core)/PCL/chitosan (shell) nanofibers (termed CS/CPT/PCL/CS), and irinotecan-coloaded liposome-incorporated PCL/chitosan-chitosan nanofibers (termed CPT@Lipo/CS/PCL/CS) in releasing irinotecan in a controlled manner and treating leukemia cancer. The fabricated formulations were characterized utilizing Fourier transform infrared analysis, transmission electron microscopy, scanning electron microscopy, dynamic light scattering, zeta potential, and polydispersity index. Irinotecan was released in a controlled manner from nanofibers filled with liposomes over 30 days. The cell viability of the fabricated nanofibrous materials toward Human umbilical vein endothelial cells (HUVECs) non-cancerous cells after 168 h was >98 % ± 1 %. The CPT@Lipo/CS/PCL/CS nanofibers achieved maximal cytotoxicity of 85 % ± 2.5 % against K562 leukemia cancer cells. The CPT@Lipo/CS/PCL/CS NFs exhibit a three-stage drug release pattern and demonstrate significant in vitro cytotoxicity. These findings indicate the potential of these liposome-incorporated core-shell nanofibers for future cancer therapy.

Microsnare retrieval as a bail-out technique of Detached Woven EndoBridge device: Illustrative series.

BACKGROUND: The Woven EndoBridge (WEB) device (MicroVention, Tustin, CA, USA) has an excellent safety profile. While major complications such as device malposition and migration are rare, they can have serious consequences if not addressed promptly. Our case series describes the safety and efficacy of Amplatz goose neck microsnare device (Medtronic in Irvine, CA, USA) in endovascular retrieval of a detached WEB device. METHODS: We retrospectively reviewed six consecutive patients who underwent endovascular WEB retrieval using Amplatz microsnare device between March 2012 and December 2022. RESULTS: All six WEB devices were successfully retrieved either directly from the aneurysm sac due to device malpositioning or from a distal branch following device migration. None of the patients experienced intra-operative aneurysm perforation, arterial dissection, or vasospasm attributable to the process of WEB extraction. Five out of six patients (83.3%) had a good functional outcome (mRS 0-1) upon discharge from the hospital and at 24 months. CONCLUSION: Our experience suggests that detached WEB devices can be safely retrieved using an Amplatz microsnare. Apart from addressing device migration, direct removal of an undersized or malpositioned WEB from the aneurysm sac appears to be a safe option that can be considered when all other rescue techniques have been exhausted.

Lateral Compression Manipulation: A Simple Approach for Sizing Taller-Than-Wide Intracranial Aneurysms with the Woven EndoBridge Device.

BACKGROUND AND PURPOSE: The Woven EndoBridge (WEB) system has established itself as a safe and effective option for managing wide-neck bifurcation aneurysms. Addressing aneurysms with a greater height than width using conventional WEB-sizing methods has proved ineffective due to the inherent configuration of the devices. To overcome this limitation, we propose an intuitive approach that involves swapping the width and height dimensions of the aneurysm to determine the appropriate WEB size. MATERIALS AND METHODS: A retrospective analysis was conducted on patients undergoing WEB embolization at a single neuroscience center from March 2013 to February 2023. RESULTS: Twenty-five eligible aneurysms were identified, with the height dimension exceeding the width by an average of 2.33 mm (ranging from 1.4 to 4.5 mm). Of these, 20 cases adhered to the recommended sizing technique, resulting in a 100% success rate of adequate occlusion (14/20 complete occlusion, 6/20 proximal recess filling). In contrast, the outcomes for the remaining 5 cases that did not follow the proposed sizing method were less favorable (P < .05). Among these, 4 cases treated with undersized WEBs showed neck remnants during follow-up, and 1 patient who received an oversized WEB required device replacement during the same procedure. CONCLUSIONS: The simple sizing method we proposed for treating taller-than-wide aneurysms has demonstrated promising results, allowing the WEB system to address twice the original size range of treatable aneurysms. Further research with a larger sample size is recommended.

Immunomodulatory effect of Myrtenol on benzo (a) pyrene-induced lung cancer in Swiss albino mice via modulation of tumor markers, cytokines and inhibition of PCNA expression.

Lung cancer is one of the most common cancers in men. Although many diagnostic and treatment regimens have been followed in the treatment for lung cancer, increasing mortality rate due to lung cancer is depressing and hence requires alternative plant based therapeutics with with less side-effects. Myrtenol exhibits anti-inflammatory and antioxidant properties. Hence we intended to study the effect of Myrtenol on B(a)P-induced lung cancer. Our study showed that B(a)P lowered hematological count, decreased phagocyte and avidity indices, nitroblue tetrazolium (NBT) reduction, levels of immunoglubulins, antioxidant levels, whereas Myrtenol treatment restored them back to normal levels. On the other hand, xenobiotic and liver dysfunction marker enzymes and pro-inflammatory cytokines were elevated on B(a)P exposure, which retuned back to normal by Myrtenol. This study thus describes the immunomodulatory and antioxidant effects of Myrtenol on B[a]P-induced immune destruction.

Precise Construction of Dual-Promising Anticancer Drugs Associated with Gold Nanomaterials on Glioma Cancer Cells.

Multiple chemodrugs with nanotechnology have proven to be an effective cancer treatment technique. When taken combined, cabazitaxel (CTX) and cisplatin (PT) have more excellent cytotoxic effects than drugs used alone in the chemotherapy of several different cancers. However, several severe side effects are associated with using these chemotherapy drugs in cancer patients. Gold nanomaterials (AuNMs) are promising as drug carriers because of their small diameter, easy surface modifications, good biocompatibility, and strong cell penetration. This work aimed to determine the CTX and PT encapsulated with AuNMs against human glioma U87 cancer cells. The fabrication of the AuNMs achieved a negative surface charge, polydispersity index, and the mean sizes. The combined cytotoxic effect of CTX and PT bound to AuNMs was greater than that of either drug alone when tested on U87 cells. The half inhibitory concentration (IC50) values for free PT were 54.7 µg/mL (at 24 h) and 4.8 g µg/mL (at 72 h). Results acquired from the MTT assay show cell growth decreases time- and concentration-dependent AuNMs, free CTX, free PT, and AuNMs@CTX/PT-induced cytotoxicity and, ultimately, the cell death of U87 cells via apoptosis. The biochemical apoptosis staining techniques investigated the cells' morphological changes of the cells (acridine orange and ethidium bromide (AO-EB) and nuclear staining (DAPI) techniques). The AO-EB and nuclear staining results reveal that the NPs effectively killed cancer cells. Furthermore, the flow cytometry analysis examined the mode of cell death. Therefore, AuNMs@CTX/PT has excellent potential in the cancer therapy of different cancer cells.

Testosterone with Silymarin Improves Diabetes-obesity Comorbidity Complications by Modulating Inflammatory Responses and CYP7A1/ACC Gene Expressions in Rats.

BACKGROUND: The co-morbidity of DMOB has become increasingly problematic among the world's population because of a high-calorie diet and sedentary lifestyle. DMOB is associated with lower testosterone (TN) levels, the male sex hormone. The phytochemical compound silymarin (SN) exerts antidiabetic activity by modifying ß-cells and anti-obesity activity by inhibiting adipogenesis by methylxanthine. AIM: The goal of this study was to find out how well testosterone (TN) with silymarin (SN) protects against oxidative stress and inflammation in the liver of the experimental rats with type 2 diabetes (T2D) and obesity (DMOB). OBJECTIVES: The present study evaluates the efficacy of TN and SN combination (TNSN) on the levels of the potential parameters, such as body mass, serum marker enzymes, fasting glucose levels, HbA1c levels, lipid profile, enzymatic and non-enzymatic antioxidants, proinflammatory cytokines, gene expression pathways, and histopathology in a DMOB comorbidity rat model. METHODS: Male Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) for 20 weeks with an administration of a single dose of streptozotocin (STZ) i.p. injection (30 mg/kg) on the 9th week of the study. The procedure was to develop the DMOB co-morbidity model in the experimental animals. Co-treatment of TN and SN administration were followed throughout the experiment. Rats were sacrificed after overnight fasting to collect serum and liver tissue samples. Samples were analyzed using a clinical chemistry automated analyzer, spectrophotometry, and quantitative real-time PCR (qPCR) methods and protocols. RESULTS: Analyses of body mass changes, serum marker enzymes, fasting glucose levels, HbA1c levels, lipid profiles, enzymatic and non-enzymatic antioxidants, TNF-α, IL-6, adiponectin, CYP7A1, ACC expression pathways, and histopathology showed significant abnormal levels (P ≤ 0.05) in the pathological group. These were efficiently treated to normal by the administration of TNSN. CONCLUSION: These results concluded that TNSN exerted protective efficacy against the liver abnormalities in the co-morbidity of the DMOB rat model.

Diterpene Coronarin Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Both In Vivo and In Vitro Models.

Acute lung injury (ALI) is a clinical condition occurs due to severe systemic inflammatory response for clinical stimulus like pneumonia, sepsis, trauma, aspiration, inhalation of toxic gases, and pancreatitis. Disruption of alveolar barriers, activation of macrophages, infiltration of neutrophils, and proinflammatory cytokines are the vital events occurs during ALI. The drugs which inhibit these inflammatory response can protect lungs from inflammatory insults. In this study, we examined the potency of phytochemical coronarin, a diterpene which have been proven to possess anti-inflammatory, antioxidant, antiangiogenic, and antitumor activities. Healthy BALB/c mice were induced to acute lung injury with intra-tracheal administration of LPS and then treated with 5 and 10 mg/kg concentration of coronarin. The wet/dry lung weight of mice were estimated to assess the induction of pulmonary edema. BALF fluid was analyzed for protein concentrations and immune cells count. Myeloperoxidase activity and levels of chemokines MCP-2 and MIP-2, iNOS, COX-2, and PGE-2 were quantified to assess the immunomodulatory effect of coronarin against LPS-induced ALI. The levels of proinflammatory cytokines was measured to examine the anti-inflammatory property of coronarin, and it was confirmed with histopathological analysis of the lung tissue. Murine RAW 264.7 cells were utilized for the in vitro analysis. Cell cytoxicity and cytoprotective property of coronarin was assessed with MTT assay in LPS-treated Murine RAW 264.7. The anti-inflammatory property of coronarin was further confirmed in in vitro condition by estimating the levels of pro-inflammatory cytokines in coronarin-treated and untreated LPS-induced cells. Overall, our in vivo and in vitro results confirm coronarin significantly inhibited the infiltration of neutrophils prevented immunodulatory activity and synthesis of proinflammatory cytokines and alleviated the acute lung injury induced by LPS. Coronarin is a potent anti-inflammatory drug which can be subjected to further research to be prescribed as drug for ALI.

Mechanistic modelling of targeted pulmonary delivery of dactinomycin iron oxide-loaded nanoparticles for lung cancer therapy.

With the increase in respiratory conditions including lung cancer post covid-19 pandemic, drug-loaded nanoparticulate dry powder inhalers (DPIs) can facilitate targeted lung delivery as a patient-friendly, non-invasive method. The aim of this work was to synthesise and optimise iron oxide nanoparticles (IONPs) containing dactinomycin as a model drug, using Quality by Design principles. Chitosan and sodium alginate were investigated as polymeric coatings. The mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), burst-effect (BE), entrapment-efficiency and the emitted-dose (ED) were investigated in initial screening studies and outcomes used to set up a Design of Experiments. Results revealed that chitosan IONPs were superior to that of sodium alginate in delivering DPI with optimal properties [ED (89.9%), FPF (59.7%), MMAD (1.59 µm) and BE (12.7%)]. Design space for targeted IONPs included formulations containing 2.1-2.5% dactinomycin and 0.5-0.9% chitosan. Differential scanning calorimetry and X-ray diffraction and SEM-EDS analysis revealed effective formation of IONPs, and TEM images revealed the production of spherical IONPs with particle size of 4.4 ± 0.77 nm. This work overcame the light sensitivity of dactinomycin to potentially target the high molecular weight drugs to the lungs, with controlled delivery based on a reduced burst effect.

Adsorption Characteristics of Hair Dyes Removal from Aqueous Solution onto Oak Cupules Powder Coated with ZnO.

Three hair dyes of Arianor madder red 306003 (R), Arian or Straw Yellow 306005 (Y), and Arianor ebony 306020 (E) were removed from an aqueous solution in a batch mode using a powder of oak cupules coated with ZnO (COZ). The COZ-adsorbent material was characterized in terms of XRD, FT-IR, and SEM analysis. The best conditions for the uptake of hair dyes by COZ were investigated. For Y dye, the best uptake was estimated on 0.06 g of COZ at 7.0 pH for 150 min. The E dye uptake requires 120 min on 0.05 g of COZ at 9.0 pH. For E hair dye, kinetic data revealed a pseudo-first-order model for E hair dye and a pseudo-second-order model for R and Y. Equilibrium data exhibited consistency with the Langmuir isotherm model for the adsorption of E dye onto COZ, and the Freundlich isotherm model for the adsorption of R and Y hair dyes onto COZ. Isotherms models of D-R and Temkin were also examined. The thermodynamic parameters (-ve ∆G and +ve ∆H and ∆S) demonstrated that the removal of hair dyes by COZ is spontaneous, endothermic, and feasible. The adsorption capacity of COZ for R, Y, and E uptake was found to be 55.5, 52.6, and 135.1 mg·g-1, respectively. Furthermore, COZ reusability was demonstrated after five cycles of regeneration, with a negligible decline in adsorption extent (13.08%, 13.85, and 10.20% for R, Y, and E, respectively) in comparison to its initial capacity.

Preparation, characterization, in vitro drug release and anti-inflammatory of thymoquinone-loaded chitosan nanocomposite.

In this study, we formulated Thymoquinone-loaded nanocomposites (TQ-NCs) using high-pressure homogenizer without sodium tripolyphosphate. The TQ-NCs were characterized and their anti-inflammatory determined by the response of the LPS-stimulated macrophage RAW 264.7 cells in the production of nitric oxide, prostaglandin E2, tumor necrosis factor-α, interleukin-6, and interleukin-1ß. The physicochemical properties of TQ-NC were determined using different machines. TQ was fully incorporated in the highly thermal stable nanoparticles. The nanoparticles showed rapid release of TQ in the acidic medium of the gastric juice. In medium of pH 6.8, TQ-NC exhibited sustained release of TQ over a period of 100 h. The results suggest that TQ-NC nanoparticles have potential application as parenterally administered therapeutic compound. TQ-NC effectively reduce production of inflammatory cytokines by the LPS-stimulated RAW 264.7 cells, indicating that they have anti-inflammatory properties. In conclusion, TQ-NC nanoparticles have the characteristics of efficient carrier for TQ and an effective anti-inflammatory therapeutic compound.

Perfusion Imaging for Endovascular Thrombectomy in Acute Ischemic Stroke Is Associated With Improved Functional Outcomes in the Early and Late Time Windows.

BACKGROUND: The impact on clinical outcomes of patient selection using perfusion imaging for endovascular thrombectomy (EVT) in patients with acute ischemic stroke presenting beyond 6 hours from onset remains undetermined in routine clinical practice. METHODS: Patients from a national stroke registry that underwent EVT selected with or without perfusion imaging (noncontrast computed tomography/computed tomography angiography) in the early (<6 hours) and late (6-24 hours) time windows, between October 2015 and March 2020, were compared. The primary outcome was the ordinal shift in the modified Rankin Scale score at hospital discharge. Other outcomes included functional independence (modified Rankin Scale score ≤2) and in-hospital mortality, symptomatic intracerebral hemorrhage, successful reperfusion (Thrombolysis in Cerebral Infarction score 2b-3), early neurological deterioration, futile recanalization (modified Rankin Scale score 4-6 despite successful reperfusion) and procedural time metrics. Multivariable analyses were performed, adjusted for age, sex, baseline stroke severity, prestroke disability, intravenous thrombolysis, mode of anesthesia (Model 1) and including EVT technique, balloon guide catheter, and center (Model 2). RESULTS: We included 4249 patients, 3203 in the early window (593 with perfusion versus 2610 without perfusion) and 1046 in the late window (378 with perfusion versus 668 without perfusion). Within the late window, patients with perfusion imaging had a shift towards better functional outcome at discharge compared with those without perfusion imaging (adjusted common odds ratio [OR], 1.45 [95% CI, 1.16-1.83]; P=0.001). There was no significant difference in functional independence (29.3% with perfusion versus 24.8% without; P=0.210) or in the safety outcome measures of symptomatic intracerebral hemorrhage (P=0.53) and in-hospital mortality (10.6% with perfusion versus 14.3% without; P=0.053). In the early time window, patients with perfusion imaging had significantly improved odds of functional outcome (adjusted common OR, 1.51 [95% CI, 1.28-1.78]; P=0.0001) and functional independence (41.6% versus 33.6%, adjusted OR, 1.31 [95% CI, 1.08-1.59]; P=0.006). Perfusion imaging was associated with lower odds of futile recanalization in both time windows (late: adjusted OR, 0.70 [95% CI, 0.50-0.97]; P=0.034; early: adjusted OR, 0.80 [95% CI, 0.65-0.99]; P=0.047). CONCLUSIONS: In this real-world study, acquisition of perfusion imaging for EVT was associated with improvement in functional disability in the early and late time windows compared with nonperfusion neuroimaging. These indirect comparisons should be interpreted with caution while awaiting confirmatory data from prospective randomized trials.

Preparation and characterisation of ciprofloxacin-loaded silver nanoparticles for drug delivery.

Silver nanoparticles (AgNPs) have shown potential applications in drug delivery. In this study, the AgNPs was prepared from silver nitrate in the presence of alginate as a capping agent. The ciprofloxacin (Cipro) was loaded on the surface of AgNPs to produce Cipro-AgNPs nanocomposite. The characteristics of the Cipro-AgNPs nanocomposite were studied by X-ray diffraction (XRD), UV-Vis, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Fourier-transform infra-red analysis (FT-IR) and zeta potential analyses. The XRD of AgNPs and Cipro-AgNPs nanocomposite data showed that both have a crystalline structure in nature. The FT-IR data indicate that the AgNPs have been wrapped by the alginate and loaded with the Cipro drug. The TEM image showed that the Cipro-AgNPs nanocomposites have an average size of 96 nm with a spherical shape. The SEM image for AgNPs and Cipro-AgNPs nanocomposites confirmed the needle-lumpy shape. The zeta potential for Cipro-AgNPs nanocomposites exhibited a positive charge with a value of 6.5 mV. The TGA for Cipro-AgNPs nanocomposites showed loss of 79.7% in total mass compared to 57.6% for AgNPs which is due to the Cipro loaded in the AgNPs. The release of Cipro from Cipro-AgNPs nanocomposites showed slow release properties which reached 98% release within 750 min, and followed the Hixson-Crowell kinetic model. In addition, the toxicity of AgNPs and Cipro-AgNPs nanocomposites was evaluated using normal (3T3) cell line. The present work suggests that Cipro-AgNPs are suitable for drug delivery.

Graphene oxide-ellagic acid nanocomposite as effective anticancer and antimicrobial agent.

In this study, ellagic acid (ELA), a skin anticancer drug, is capped on the surface(s) of functionalised graphene oxide (GO) nano-sheets through electrostatic and π-π staking interactions. The prepared ELA-GO nanocomposite have been thoroughly characterised by using eight techniques: Fourier-transform infrared spectroscopy (FTIR), zeta potential, X-ray diffraction (XRD), thermogravimetric analysis (TGA), Raman spectroscopy, atomic force microscopy (AFM) topographic imaging, transmission electron microscopy (TEM), and surface morphology via scanning electron microscopy (SEM). Furthermore, ELA drug loading and release behaviours from ELA-GO nanocomposite were studied. The ELA-GO nanocomposite has a uniform size distribution averaging 88 nm and high drug loading capacity of 30 wt.%. The in vitro drug release behaviour of ELA from the nanocomposite was investigated by UV-Vis spectrometry at a wavelength of λmax 257 nm. The data confirmed prolonged ELA release over 5000 min at physiological pH (7.4). Finally, the IC50 of this ELA-GO nanocomposite was found to be 6.16 µg/ml against B16 cell line; ELA and GO did not show any cytotoxic effects up to 50 µg/ml on the same cell lines.

Chlorambucil-Iron Oxide Nanoparticles as a Drug Delivery System for Leukemia Cancer Cells.

INTRODUCTION: Traditional cancer therapies may have incomplete eradication of cancer or destroy the normal cells. Nanotechnology solves the demerit by a guide in surgical resection of tumors, targeted chemotherapies, selective to cancerous cells, etc. This new technology can reduce the risk to the patient and automatically increased the probability of survival. Toward this goal, novel iron oxide nanoparticles (IONPs) coupled with leukemia anti-cancer drug were prepared and assessed. METHODS: The IONPs were prepared by the co-precipitation method using Fe+3/Fe+2ratio of 2:1. These IONPs were used as a carrier for chlorambucil (Chloramb), where the IONPs serve as the cores and chitosan (CS) as a polymeric shell to form Chloramb-CS-IONPs. The products were characterized using transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) analysis, Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM) analyses, and thermal gravimetric analysis (TGA). RESULTS: The as-prepared IONPs were found to be magnetite (Fe3O4) and were coated by the CS polymer/Chloramb drug for the formation of the Chloramb-CS-IONPs. The average size for CS-IONPs and Chloramb-CS-IONPs nanocomposite was found to be 15 nm, with a drug loading of 19% for the letter. The release of the drug from the nanocomposite was found to be of a controlled-release manner with around 89.9% of the drug was released within about 5000 min and governed by the pseudo-second order. The in vitro cytotoxicity studies of CS-IONPs and Chloramb-CS-IONPs nanocomposite were tested on the normal fibroblast cell lines (3T3) and leukemia cancer cell lines (WEHI). Chloramb in Chloramb-CS-IONPs nanocomposite was found to be more efficient compared to its free form. CONCLUSION: This work shows that Chloramb-CS-IONPs nanocomposite is a promising candidate for magnetically targeted drug delivery for leukemia anti-cancer agents.

A Statistical Study on the Development of Metronidazole-Chitosan-Alginate Nanocomposite Formulation Using the Full Factorial Design.

The goal of this study was to develop and statistically optimize the metronidazole (MET), chitosan (CS) and alginate (Alg) nanoparticles (NP) nanocomposites (MET-CS-AlgNPs) using a (21 × 31 × 21) × 3 = 36 full factorial design (FFD) to investigate the effect of chitosan and alginate polymer concentrations and calcium chloride (CaCl2) concentration ondrug loading efficiency(LE), particle size and zeta potential. The concentration of CS, Alg and CaCl2 were taken as independent variables, while drug loading, particle size and zeta potential were taken as dependent variables. The study showed that the loading efficiency and particle size depend on the CS, Alg and CaCl2 concentrations, whereas zeta potential depends only on the Alg and CaCl2 concentrations. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and in vitro drug release studies. XRD datashowed that the crystalline properties of MET changed to an amorphous-like pattern when the nanocomposites were formed.The XRD pattern of MET-CS-AlgNPs showed reflections at 2θ = 14.2° and 22.1°, indicating that the formation of the nanocompositesprepared at the optimum conditions havea mean diameter of (165±20) nm, with a MET loading of (46.0 ± 2.1)% and a zeta potential of (-9.2 ± 0.5) mV.The FTIR data of MET-CS-AlgNPs showed some bands of MET, such as 3283, 1585 and 1413 cm-1, confirming the presence of the drug in the MET-CS-AlgNPs nanocomposites. The TGA for the optimized sample of MET-CS-AlgNPs showed a 70.2% weight loss compared to 55.3% for CS-AlgNPs, and the difference is due to the incorporation of MET in the CS-AlgNPs for the formation of MET-CS-AlgNPs nanocomposites. The release of MET from the nanocomposite showed sustained-release properties, indicating the presence of an interaction between MET and the polymer. The nanocomposite shows a smooth surface and spherical shape. The release profile of MET from its MET-CS-AlgNPs nanocomposites was found to be governed by the second kinetic model (R2 between 0.956-0.990) with more than 90% release during the first 50 h, which suggests that the release of the MET drug can be extended or prolonged via the nanocomposite formulation.

Characterization of thymoquinone/hydroxypropyl-ß-cyclodextrin inclusion complex: Application to anti-allergy properties.

Thymoquinone is an effective phytochemical compound in the treatment of various diseases. However, its practical administration has been limited due to poor aqueous solubility and bioavailability. In this work, we developed a novel inclusion complex of thymoquinone and hydroxypropyl-ß-cyclodextrin that features improved solubility and bioactivity. The drug solubility was markedly accelerated in the increasing ratio of hydroxypropyl-ß-cyclodextrin to thymoquinone amount. The formation of the thymoquinone/hydroxypropyl-ß-cyclodextrin inclusion complex was evidenced using X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, Fourier transform infrared, scanning electron microscopy and nuclear magnetic resonance. The release behavior of the complex, as well as of their mixtures, was examined in artificial gastric (pH 1.2) and intestinal (pH 6.8) dissolution media. The formulated complex released the drug rapidly at the initial stage, followed by a slow release. Thermodynamic parameters ΔH, ΔS and ΔG were calculated with temperatures ranging from 20 to 45 °C to evaluate the complexation process. The activity of the inclusion complex was evaluated on IgE-mediated allergic response in rat basophilic leukemia (RBL-2H3) cells by monitoring key allergic mediators. The results revealed that compared with free thymoquinone, the inclusion complex more strongly inhibited the release of histamine, tumor necrosis factor-α, and interleukin-4, and was not cytotoxic at the tested thymoquinone concentrations (0.125-4 µg/mL) indicating the inclusion complex possibly had better antiallergic effects. Our finding suggested that the inclusion complex achieved prolonged action and reduced side-effect of thymoquinone.

Association of Low B Cell Count and IgG Levels With Infection, and Poor Vaccine Response With All-Cause Mortality in an Immunosuppressed Vasculitis Population.

OBJECTIVE: Patients with systemic vasculitis (SV) have an increased risk of all-cause mortality, often due to infection, compared to the healthy population. We investigated whether humoral response to vaccination and biomarkers of immune dysfunction were associated with infection and death. METHODS: Patients with SV in remission were vaccinated with pneumococcal 7-valent conjugate, Haemophilus influenzae type b, and meningococcal group C conjugate vaccine and meningococcal polysaccharide groups A, C, Y, and W135 vaccines. Total IgG and antibody titers against specific antigens and lymphocyte subset analysis were performed before vaccination. Postvaccination antibody titers were measured at 4 weeks and 2 years, from which an antibody response score was calculated. Infections and death following vaccination were collected prospectively following vaccination. RESULTS: A total of 92 patients were safely vaccinated with no increase in disease relapse, median followup 4.6 years (interquartile range [IQR] 3.6-4.8 years). Eighteen patients died at a median of 2 years and the overall infection rate was 0.4 (IQR 0.2-1.3) infections/patient/year. Reduced serum IgG, B cell count, and CD4+ cell counts predicted poor vaccine response and infection but not death. The response rates to individual vaccine antigens was highly variable, with a median response rate of 46% (IQR 39-58%) of patients responding to each individual antigen. Vaccine response, age, and reduced renal function were independent predictors of all-cause mortality in multivariate analysis. CONCLUSION: Total IgG and B cell counts predict infection and response to vaccination. Vaccination in patients with SV in remission is safe and the response predicts all-cause mortality. Vaccine response is a surrogate marker of immune system health.