Preparation and Characterization of Modified Polyethyleneimine Magnetic Nanoparticles for Cancer Drug Delivery

Magnetic nanoparticles with polymeric coating have great significance in drug delivery purpose. We intended to prepare a modified amphiphilic polymer with targeting susceptibility to reduce side effects to normal cells. In this study polyethyleneimine (PEI) as a polycationic polymer reacted with sebacoyl chloride to make a new amphiphilic polymer and folic acid as a targeting agent to reduce cytotoxicity of polymer and increase specific entrance of nanoparticles to cancerous cells. The obtained polymer (PEI-Sb-FA) was then coated on magnetic nanoparticles (MNPs) to stabilize them. The core-shell nanoparticles were characterized by different methods such as scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and vibrating sample magnetometer (VSM). Curcumin was finally loaded on PEI-Sb-FA-MNPs and the release behavior was studied in different pH. Curcumin loading of 28.2% was obtained and released drug in acidic pH = 4.5 was more than pH = 7.4, showing drug release sensitivity toward pH of media

Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

Abstract: Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met) with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer

Poly-l-lactic acid scaffold incorporated chitosan-coated mesoporous silica nanoparticles as pH-sensitive composite for enhanced osteogenic differentiation of human adipose tissue stem cells by dexamethasone delivery

Nowadays, the development of drug-loaded electrospun organic-inorganic composite scaffolds for tissue engineering application is an attractive approach. In this study, a composite scaffold of Poly-l-lactic acid (PLLA) incorporated dexamethasone (Dexa) loaded Mesoporous Silica Nanoparticles (MSN) coated with Chitosan (CS) were fabricated by electrospinning for bone tissue engineering application. The MSN was prepared by precipitation method. After that, Dexamethasone (Dexa) was loaded into MSNs (MSN-Dexa). In the following, CS was coated over the prepared nanoparticles to form MSN-Dexa@CS and then, were mixed to PLLA solution to form MSN-Dexa@CS/PLLA composite for electrospinning. The surface morphology, hydrophilicity, tensile strength and the bioactivity of the scaffolds were characterized. The osteogenic proliferation and differentiation potential were evaluated by MTT assay and by measuring the basic osteogenic markers: the activity of the enzyme alkaline phosphatase and the level of calcium deposition. The composite scaffolds prepared here have conductive surface property and have a better osteogenic potential than pure PLLA scaffolds. Hence, the controlled release of nanoparticle containing Dexa from composite scaffold supported the osteogenesis and made the composite scaffolds ideal candidates for bone tissue engineering application and pH-sensitive delivery of drugs at the site of implantation in tissue regeneration. Keywords Author Keywords:Mesoporous silica nanoparticles; electrospinning; Poly-l-lactic acid; chitosan; dexamethasone; composite scaffold; bone tissue engineering KeyWords Plus:DRUG-DELIVERY; BONE; SYSTEM; NANOFIBERS; SURFACE; POLY(L-LACTIDE); PROLIFERATION; CARTILAGE; RELEASE; PEPTID

Coumarin derivatives bearing benzoheterocycle moiety: synthesis, cholinesterase inhibitory, and docking simulation study

Objective(s): To investigate the efficiency of a novel series of coumarin derivatives bearing benzoheterocycle moiety as novel cholinesterase inhibitors. Materials and Methods: Different 7-hydroxycoumarin derivatives were synthesized via Pechmann or Knoevenagel condensation and conjugated to different benzoheterocycle (8-hydroxyquinoline, 2-mercaptobenzoxazole or 2-mercaptobenzimidazole) using dibromoalkanes 3a-m. Final compounds were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) by Ellman's method. Kinetic study of AChE inhibition and ligand-protein docking simulation were also carried out for the most potent compound 3b. Results: Some of the compounds revealed potent and selective activity against AChE. Compound 3b containing the quinoline group showed the best activity with an IC50 value of 8.80 µM against AChE. Kinetic study of AChE inhibition revealed the mixed-type inhibition of the enzyme by compound 3b. Ligand-protein docking simulation also showed that the flexibility of the hydrophobic five carbons linker allows the quinoline ring to form π-π interaction with Trp279 in the PAS. Conclusion: We suggest these synthesized compounds could become potential leads for AChE inhibition and prevention of AD symptoms

One-pot, four-component synthesis of novel cytotoxic agents 1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines

A series of N-benzyl-1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines were synthesized via one-pot reaction of appropriate benzylamine, pyrrole-2-carbaldehyde, (N-isocyanimino)triphenylphosphorane, and a carboxylic acid. The anti-tumor potential of title compounds was tested against several cancer cell lines by using MTT assay. Some tested compounds including 5e, 5p and 5q exhibited comparable or better cytotoxic activity against A549, HT29 or HT1080 cells in comparison to the reference drug doxorubicin. Also, the cytotoxic activity of compounds 5d and 5n against MCF-7 was better than that of doxorubicin. Compound 5n with IC50 value of 4.3 mM was 4-fold more potent than doxorubicin. The structureeactivity relationship study revealed that the introduction of halogen atoms on both 5-phenyl ring and N-benzyl part improved the cytotoxic activity against all tested cell lines

Synthesis and Characterization of Silk Fibroin- Coated Mesoporous Silica Nanoparticles for Tioguanine Targeting to Leukemia

Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this work, large pore size MSNs were prepared by the co-condensation method. Tioguanine (TG) as a hydrophobic drug was loaded into the synthesized MSNs to prepare TG@MSNs. The results show MSNs were successfully synthesized and they have good loading efficiency and capacity for TG. Silk fibroin (SF) as an active targeting agent and pH-sensitive targeting release, is a natural protein from silkworm cocoons. It was used to coating MSNs to prepare SF/TG@MSNs. SF was Degummed and it was characterized by nuclear magnetic resonance (NMR), fourier transform infrared (FTIR) and field emission scanning electron microscopy (FESEM) methods. The MSNs were fully characterized by FESEM, transmission electron microscopy (TEM), zeta potential analysis, dynamic light scattering (DLS), nitrogen adsorption/desorption analysis, thermogravimetric analysis (TGA), X-ray diffraction (XRD) analysis, FTIR and UV-visible spectroscopies. The mechanism of TG release from SF/TG@MSNs were pH-sensitive. The in vitro release modeling revealed that TG released via the Higuchi model with fickian diffusion mechanism. In conclusion, SF/TG@MSNs exhibited a well synthesized and good payload for use in targeted drug delivery for leukemia

Conjugated Linoleic Acid-Curcumin Attenuates Cognitive Deficits and Oxidative Stress Parameters in the Ethidium Bromide�Induced Model of Demyelination

Oxidative stress has been shown to play an important role in the pathogenesis of multiple sclerosis (MS). Curcumin (CUR), an antioxidant compound, can be a potent treatment for neurodegenerative diseases, such as MS. CUR has poor bioavailability; therefore, it is used in nanoforms to increase its bioavailability. In the present study, the effects of CUR and conjugated linoleic acid-CUR (Lino-CUR) on spatial memory and oxidative stress in a putative animal model of MS were investigated. Forty-nine adult male Wistar rats (250 ± 50 g) were randomly divided into seven groups (n = 7): control, sham, ethidium bromide (EB), CUR (20 and 40 μg/kg) + EB, and Lino-CUR (20 and 40 μg/kg) + EB groups. Following MS induction, the groups were treated for 5 consecutive days. Finally, spatial memory and levels of oxidative stress parameters were assessed. Treatment with CUR and Lino-CUR at two doses significantly improved spatial memory and reduced oxidative stress parameters in the experimental models of MS. Furthermore, the effects of high dose (40 μg/kg) of Lino-CUR were more remarkable. These findings suggest that the microinjection of CUR in its synthetic form Lino-CUR significantly ameliorated spatial memory, through the reduction of oxidative stress markers in the brain of studied animals as a rat model of MS

Degradation of Tetracycline Using a Magnetic Gadolinium-Decorated Nanoplatform: A Peroxidase Biomimetic System with Fenton-Like Catalysis

Pharmaceutical pollutants such as tetracycline (TC) pose a growing global threat to aquatic and terrestrial biodiversity. Developing new methods for the degradation of these pollutants would be a significant advancement in their management. The progress in the development of synthetic enzymes based on nanomaterials has resulted in their replacement for natural enzymes with higher performance quality. In this work, a magnetite/Gd3+/β-cyclodextrin nanoplatform was prepared and used for TC degradation for the first time. The characterization studies were carried out using various methods, including SEM, XRD, and FTIR. The peroxidase-mimic activity of the synthesized nanoplatform was evaluated using a colorimetric assay. Kinetic parameters, including Km and Vmax, were obtained using TMB (3,3′,5,5′-tetramethylbenzidine) and H2O2. The results indicated that prepared particles had a lower Km value than horseradish peroxidase (HRP), which confirmed the higher affinity of the prepared nanoplatform toward its substrates. We also demonstrated that our recyclable nanoplatform (3 mg/mL) was able to degrade 82% of TC (4.5 mM) in 85 min without any initiator such as light or ultrasonic waves. Collectively, these results confirmed the high affinity of the synthesized nanoplatform toward desired substrates, including TC

Reliable differentiation of necrosis and active metabolically contours of glioblastoma multiforme using susceptibility-based imaging

Purpose: Gadolinium-enhancing necrosis in glioblastoma multiforme (GBM), as an occasionally occurring false positive in contrast enhancement (CE) imaging, leads to trouble for segmentation of GBM and treatment. Therefore, the investigation of complementary detection way to identify the metabolically active volume of the tumor with high reliability is very worth to be addressed. Here, we reported on a case of GBM with gadolinium-enhancing necrosis in an experimental CE imaging study in mice and evaluated the discrimination of the necrosis and metabolically active parts of the GBM using conventional and state-of-the-art susceptibility-based MRI. Methods: In this study, following 5-aminolevulinic acid (ALA) and iron supplements (FAC, 6 h after ALA, intra-tumoral injection) to animal, T2*-W imaging and quantitative susceptibility mapping (QSM) were performed, and compared with CE imaging. Results: The signal intensity (SI) of the active and necrosis areas of the case in the CE image demonstrated no significant difference while the SI on the T2*-W images and susceptibility value in QSM changed 24 and 150%, respectively. Conclusion: The preclinical case report provides valuable insights into the potential of susceptibility-based MRI using ALA + FAC to apply as a robust discriminator between necrotic and viable tumors