Utilizing magnetic xanthan gum nanocatalyst for the synthesis of acridindion derivatives via functionalized macrocycle Thiacalix[4]arene.

An effective method for synthesizing acridinedione derivatives using a xanthan gum (XG), Thiacalix[4]arene (TC4A), and iron oxide nanoparticles (IONP) have been employed to construct a stable composition, which is named Thiacalix[4]arene-Xanthan Gum@ Iron Oxide Nanoparticles (TC4A-XG@IONP). The process used to fabricate this nanocatalyst includes the in-situ magnetization of XG, its amine modification by APTES to get NH2-XG@IONP hydrogel, the synthesis of TC4A, its functionalization with epichlorohydrine, and eventually its covalent attachment onto the NH2-XG@IONP hydrogel. The structure of the TC4A-XG@IONP was characterized by different analytical methods including Fourier-transform infrared spectroscopy, X-Ray diffraction analysis (XRD), Energy Dispersive X-Ray, Thermal Gravimetry analysis, Brunauer-Emmett-Teller, Field Emission Scanning Electron Microscope and Vibration Sample Magnetomete. With magnetic saturation of 9.10 emu g-1 and ~ 73% char yields, the TC4As-XG@IONP catalytic system demonstrated superparamagnetic property and high thermal stability. The magnetic properties of the TC4A-XG@IONP nanocatalyst system imparted by IONP enable it to be conveniently isolated from the reaction mixture by using an external magnet. In the XRD pattern of the TC4As-XG@IONP nanocatalyst, characteristic peaks were observed. This nanocatalyst is used as an eco-friendly, heterogeneous, and green magnetic catalyst in the synthesis of acridinedione derivatives through the one-pot pseudo-four component reaction of dimedone, various aromatic aldehydes, and ammonium acetate or aniline/substituted aniline. A combination of 10 mg of catalyst (TC4A-XG@IONP), 2 mmol of dimedone, and 1 mmol of aldehyde at 80 °C in a ethanol at 25 mL round bottom flask, the greatest output of acridinedione was 92% in 20 min.This can be attributed to using TC4A-XG@IONP catalyst with several merits as follows: high porosity (pore volume 0.038 cm3 g-1 and Pore size 9.309 nm), large surface area (17.306 m2 g-1), three dimensional structures, and many catalytic sites to active the reactants. Additionally, the presented catalyst could be reused at least four times (92-71%) with little activity loss, suggesting its excellent stability in this multicomponent reaction. Nanocatalysts based on natural biopolymers in combination with magnetic nanoparticles and macrocycles may open up new horizons for researchers in the field.

In vitro cytotoxicity and anti-cancer drug release behavior of methionine-coated magnetite nanoparticles as carriers.

A novel and specific drug delivery for in vitro cancer targeted are developed successfully by a simple one-step method. A CoFe2O4@Methionine core-shell nanoparticle was prepared by the reflux assay which amino acid in the surface makes ferrite biocompatible, enhances its chemical stability, and improves the drug-loading capacity. The synthesized nanoparticles were characterized using FTIR, TGA, XRD, SEM, TEM, and VSM which coating amino acid on the surface of CoFe2O4 was confirmed by XRD and TGA. The appearance of a new peak for C≡N confirms the formation of Letrozole-loaded carrier in the FTIR. The vibrating sample magnetometer of both bare CoFe2O4 and Methionine-coated CoFe2O4 nanoparticles exhibited room-temperature superparamagnetic behavior with a saturation value of 46 emu/g and 16.8 emu/g, respectively. The morphology and size of samples were characterized by SEM and TEM that the average size of the particle was around 28-29 nm. The loading of Letrozole and the effect of pH (5, 7.4) on the release behavior of the carrier was studied. The result of the drug release in pH is equal to 5 was about 88% which higher than pH is equal to 7.4. Also, the preparation had been evaluated for determining its cytotoxicity using MCF-7, MDA-MB-231, and MCF10A cells as an in vitro model, and the result vitro experiments showed that CoFe2O4@Methionine could significantly reduce cancer in cells model. These results demonstrate that core-shell nanoparticle was prepared is biocompatible and have potential use as drug delivery.

Multifunctional Tetracycline-Loaded Silica-Coated Core-Shell Magnetic Nanoparticles: Antibacterial, Antibiofilm, and Cytotoxic Activities.

In the current study, the physicochemical and biological properties of tetracycline-loaded core-shell nanoparticles (Tet/Ni0.5Co0.5Fe2O4/SiO2 and Tet/CoFe2O4/SiO2) were investigated. The antibacterial activity of nanoparticles alone and in combination with tetracycline was investigated against a number of Gram-positive and Gram-negative bacteria for determining minimum inhibitory concentration (MIC) values. The MIC of Tet/Ni0.5Co0.5Fe2O4/SiO2 nanoparticles turned out to be significantly higher than that of Tet/CoFe2O4/SiO2 nanoparticles. Furthermore, Tet/Ni0.5Co0.5Fe2O4/SiO2 nanoparticles exhibited potent antibiofilm activity against pathogenic bacteria compared to Tet/CoFe2O4/SiO2 nanoparticles. The drug delivery potential of both carriers was assessed in vitro up to 124 h at different pH levels and it was found that the drug release rate was increased in acidic conditions. The cytotoxicity of nanoparticles was evaluated against a skin cancer cell line (melanoma A375) and a normal cell line (HFF). Our findings showed that Tet/Ni0.5Co0.5Fe2O4/SiO2 had greater cytotoxicity than CoFe2O4/SiO2 against the A375 cell line, whereas both synthesized nanoparticles had no significant cytotoxic effects on the normal cell line. Nonetheless, the biocompatibility of nanoparticles was assessed in vivo and the interaction of nanoparticles with the kidney was scrutinized up to 14 days. The overall results of the present study implied that the synthesized multifunctional magnetic nanoparticles with drug delivery potential, anticancer activity, and antibacterial activity are promising for biomedical applications.

Super Magnetic Niosomal Nanocarrier as a New Approach for Treatment of Breast Cancer: A Case Study on SK-BR-3 and MDA-MB-231 Cell Lines.

In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe2O4 core was coated by a thin layer of silica, followed by a niosomal structure, allowing us to load letrozole and curcumin into the silica layer and niosomal layer, respectively, and investigate their synergic effects on breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different breast cancer cell lines. The cytotoxicity of the letrozole/curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular, NiCoFe2O4@L-Silica-L@C-Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3 breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in breast cancer cells, where downregulation was observed for the Bcl-2, MMP 2, MMP 9, cyclin D, and cyclin E genes while upregulation of the expression of the Bax, caspase-3, and caspase-9 genes was observed. The flow cytometry results also revealed that NiCoFe2O4@L-Silica-L@C-Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of theranostic agents.

Enhanced Antibacterial Activity of Echinacea angustifolia Extract against Multidrug-Resistant Klebsiella pneumoniae through Niosome Encapsulation.

With the increased occurrence of antibiotic-resistant bacteria, alternatives to classical antibiotics are urgently needed for treatment of various infectious diseases. Medicinal plant extracts are among the promising candidates due to their bioactive components. The aim of this study was to prepare niosome-encapsulated Echinacea angustifolia extract and study its efficacy against multidrug-resistant Klebsiella pneumoniae strains. Encapsulation was first optimized by Design of Experiments, followed by the empirical study. The obtained niosomes were further characterized for the size and morphology using dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Spherical niosomes had a diameter of 142.3 ± 5.1 nm, as measured by DLS. The entrapment efficiency (EE%) of E. angustifolia extract reached up to 77.1% ± 0.3%. The prepared niosomes showed a controlled drug release within the tested 72 h and a storage stability of at least 2 months at both 4 and 25 °C. The encapsulated E. angustifolia displayed up to 16-fold higher antibacterial activity against multidrug-resistant K.pneumoniae strains, compared to the free extract. Additionally, the niosome exhibited negligible cytotoxicity against human foreskin fibroblasts. We anticipate that the results presented herein could contribute to the preparation of other plant extracts with improved stability and antibacterial activity, and will help reduce the overuse of antibiotics by controlled release of natural-derived drugs.

Preparation, Optimization and In-Vitro Evaluation of Curcumin-Loaded Niosome@calcium Alginate Nanocarrier as a New Approach for Breast Cancer Treatment.

Cancer is one of the most common causes of mortality, and its various treatment methods can have many challenges for patients. As one of the most widely used cancer treatments, chemotherapy may result in diverse side effects. The lack of targeted drug delivery to tumor tissues can raise the possibility of damage to healthy tissues, with attendant dysfunction. In the present study, an optimum formulation of curcumin-loaded niosomes with a calcium alginate shell (AL-NioC) was developed and optimized by a three-level Box-Behnken design-in terms of dimension and drug loading efficiency. The niosomes were characterized by transmission electron microscopy, Fourier-transform infrared spectroscopy, and dynamic light scattering. The as-formulated niosomes showed excellent stability for up to 1 month at 4 °C. Additionally, the niosomal formulation demonstrated a pH-dependent release; a slow-release profile in physiological pH (7.4), and a more significant release rate at acidic conditions (pH = 3). Cytotoxicity studies showed high compatibility of AL-NioC toward normal MCF10A cells, while significant toxicity was observed in MDA-MB-231 and SKBR3 breast cancer cells. Gene expression studies of the cancer cells showed downregulation of Bcl2, cyclin D, and cyclin E genes, as well as upregulation of P53, Bax, caspase-3, and caspase-9 genes expression following the designed treatment. Flow cytometry studies confirmed a significant enhancement in the apoptosis rate in the presence of AL-NioC in both MDA-MB-231 and SKBR3 cells as compared to other samples. In general, the results of this study demonstrated that-thanks to its biocompatibility toward normal cells-the AL-NioC formulation can efficiently deliver hydrophobic drugs to target cancer cells while reducing side effects.