Magnesium whitlockite nanoparticles: Hydrothermal synthesis, anti-inflammatory and anti-cancer potential.

This study revealed the potential of magnesium whitlockite [WH: Ca18Mg2(HPO4)2(PO4)12] nanoparticles (WH NPs) for anti-inflammatory and anti-cancer therapies. Although magnesium whitlockite possesses promising biological properties, its effects on inflammation and cancer remain unexplored. In this study, we address this gap by synthesizing WH NPs and demonstrating their multifaceted functionalities. Through detailed characterization, we revealed the synthesis pathway involving brushite as a precursor, with magnesium ions incorporated during hydrothermal treatment. WH NPs exhibited anti-inflammatory properties by significantly reducing the production of key inflammatory markers (NO, TNF-α, and IL-6). Furthermore, they display promising anti-cancer activity by inhibiting the proliferation of MDA-MB-231 breast cancer cells. Our findings not only establish a deeper understanding of WH NP synthesis but also highlight their potential for the development of innovative cancer and inflammatory treatments.

Chia nanoemulsion: anti-inflammatory mechanism, biological behavior and cellular interactions.

Aim: This study explores chia oil, rich in ω-3 fatty acids and nutraceutical components, as a potential remedy for diseases, especially those linked to inflammation and cancer. Methods/materials: A chia oil-based nanoemulsion, developed through single emulsification, underwent comprehensive analysis using various techniques. In vitro and in vivo assays, including macrophage polarization, nitrite and cytokine production, cellular uptake and biodistribution, were conducted to assess the anti-inflammatory efficacy. Results & conclusion: Results reveal that the chia nanoemulsion significantly inhibits inflammation, outperforming pure oil with twice the efficacy. Enhanced uptake by macrophage-like cells and substantial accumulation in key organs indicate its potential as an economical and effective anti-inflammatory nanodrug, addressing global economic and health impacts of inflammation-related diseases.

Nanoceria Anti-inflammatory and Antimicrobial Nanodrug: Cellular and Molecular Mechanism of Action.

INTRODUCTION: Nanoceria is a well-known nanomaterial with various properties, including antioxidant, proangiogenic, and therapeutic effects. Despite its potential, there are still aspects that require further exploration, particularly its anti-inflammatory and antimicrobial activities. METHOD: The global demand for novel anti-inflammatory and antimicrobial drugs underscores the significance of understanding nanoceria in both contexts. In this study, we evaluated the effect of nanoceria on macrophage polarization to better understand its anti-inflammatory effects. Additionally, we investigated the mechanism of action of nanoceria against Cryptococcus neoformans (ATCC 32045), Candida parapsilosis (ATCC 22019), Candida krusei (ATCC 6258), and Candida albicans. RESULT: The results demonstrated that nanoceria can polarize macrophages toward an anti-inflammatory profile, revealing the cellular mechanisms involved in the anti-inflammatory response. Concerning the antimicrobial effect, it was observed that nanoceria have a more pronounced impact on Candida parapsilosis, leading to the formation of pronounced pores on the surface of this species. CONCLUSION: Finally, biochemical analysis revealed transitory alterations, mainly in liver enzymes. The data support the use of nanoceria as a potential anti-inflammatory and antimicrobial drug and elucidate some of the mechanisms involved, shedding light on the properties of this nanodrug.

Micellar solution of [223Ra]RaCl2: Reaching renal excretion, potent efficacy in osteoblastic osteosarcoma in PDX model, biochemistry alterations and pharmacokinetics.

Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.

Methyl gallate nanomicelles impairs neutrophil accumulated in zymosan-induced arthritis.

Arthritis is a chronic disease that affects, approximately, 1 % of the total global population. It is characterized by chronic inflammation, accompanied in most of the cases of motor disability and sever pain. The main therapies available have high risk of failure and advanced treatments are scarce and highly cost. In this scenario, search for effective, safe and low-cost treatments is quite desirable. Methyl gallate (MG) is a plant-derived phenolic compound described to present remarkable anti-inflammatory effect in experimental models of arthritis. Thus, in this study we formulated nanomicelles of MG using Pluronic (F-127) as matrix and evaluated in vivo the pharmacokinetic, biodistribution and its effect in the mice model of zymosan-induced arthritis. The nanomicelles were formed with a size 126 nm. The biodistribution showed a ubiquitous tissue deposition with a renal excretion. The pharmacokinetics showed elimination half-life of 1.72 h and a clearance of 0.006 L/h. The oral pretreatment with nanomicelles containing MG (3.5 or 7 mg/kg) demonstrated a reduction in total leukocytes, neutrophils, and mononuclear cells from the inflammation site. The data supports the use of methyl gallate nanomicelles as an alternative drug for arthritis. DATA AVAILABILITY: All the data of this study are transparent.

The Impact of Radiolabeled Nanomaterials.

Nanotechnology has changed the world, with a great impact on industry and medicine. In this commentary, we discuss the importance of radiolabeled nanomaterials for the construction of theranostic, imaging and therapeutic agents in order to pave the future of medicine.

pH-Sensitive Degradable Oxalic Acid Crosslinked Hyperbranched Polyglycerol Hydrogel for Controlled Drug Release.

pH-sensitive degradable hydrogels are smart materials that can cleave covalent bonds upon pH variation, leading to their degradation. Their development led to many applications for drug delivery, where drugs can be released in a pH-dependent manner. Crosslinking hyperbranched polyglycerol (HPG), a biocompatible building block bearing high end-group functionality, using oxalic acid (OA), a diacid that can be synthesized from CO2 and form highly activated ester bonds, can generate this type of smart hydrogel. Aiming to understand the process of developing this novel material and its drug release for oral administration, its formation was studied by varying reactant stoichiometry, concentration and cure procedure and temperature; it was characterized regarding gel percent (%gel), swelling degree (%S), FTIR and thermal behavior; impregnated using ibuprofen, as a model drug, and a release study was carried out at pH 2 and 7. Hydrogel formation was evidenced by its insolubility, FTIR spectra and an increase in Td and Tg; a pre-cure step was shown to be crucial for its formation and an increase in the concentration of the reactants led to higher %gel and lower %S. The impregnation resulted in a matrix-encapsulated system; and the ibuprofen release was negligible at pH 2 but completed at pH 7 due to the hydrolysis of the matrix. A pH-sensitive degradable HPG-OA hydrogel was obtained and it can largely be beneficial in controlled drug release applications.

Ionizing Radiation: Chemical Kinetics, Chemical Bounds, and Radiation Chemistry on Polymers.

Ionizing radiation has been used for decades and expanded to several applications in multivariate sectors, becoming an important tool to promote controlled chemical reactions in polymeric structures, according to their chemical properties for developing new materials. In addition, the use of radiation can also be applied in order to reduce or eliminate compounds from solutions that may be harmful or of low interest. In this review, we overviewed the chemistry behind material irradiation and the attractive use of ionizing radiation in scientific and industrial development. In this regard, the review was divided into three main sections titled (1) chemical kinetics intermediated by radiation, (2) chemical bonds intermediated by radiation, and (3) radiation chemistry on polymers. We concluded that graft polymerization, crosslinking and chain scission reactions induced by ionizing radiation are very efficient and green strategies for developing new materials with improved properties. Furthermore, water radiolysis plays a key role in the degradation of several contaminants, including pharmaceuticals and microplastics, in aqueous solutions. However, more studies must be conducted to complement the existing theory about the proposed mechanisms responsible for modifying the chemical, mechanical, thermal, optical, and so forth properties of irradiated materials.

Hemostatic changes in patients undergoing hemodialysis: Differences between central venous catheters and arterio-venous fistulas.

BACKGROUND: Failure to mature the fistula in patients undergoing hemodialysis leads to prolonged use of the central venous catheter (CVC) and can compromise the patency of the catheter and the arteriovenous fistula (AVF) due to thrombus development. OBJECTIVE: To evaluate hemostatic changes in patients undergoing hemodialysis with prolonged use of CVC or AVF. METHOD: Cross-sectional study with a total of 200 adult participants who were divided into the following groups: I:control; II: patients who had 5-8 months of CVC insertion; III: patients who had 9-36 months of insertion; IV patients who had 5-8 months of AVF; and V: patients who had 9-36 months of AVF. Platelet activation was investigated by expressions of GPIIb/IIIa and p-selectin using flow cytometry. The Elisa-thrombomodulin (TM) test was used to compare groups III and V. RESULTS: The p-selectin percentage expression of group I was 15.30 (12.30-16.80), II 23.25 (20.75-30.55); and III 54.00 (44.75-59.29) were significant (p < 0.001). Groups I, IV, and V were also significant (p < 0.001). The median fluorescence for GPIIb/IIIa for groups I, II, and III were significant (p < 0.0001). As for the Elisa test, an increased absorbance of TM was verified in patients who used the CVC 4372 (3951-4733) compared with those patients who used the AVF 2162 (1932-2485) (p < 0.0001). CONCLUSION: It can be concluded that CVC patients had a larger platelet expression of GPIIb/IIIa and p-selectin than AVF patients. The high concentration of TM in CVC patients may suggest a greater stimulation of the intrinsic than extrinsic coagulation pathways.