Design, Preparation and In Vitro Evaluation of Core-Shell Fused Deposition Modelling 3D-Printed Verapamil Hydrochloride Pulsatile Tablets.

The aim of the study was to investigate core-shell pulsatile tablets by combining the advantages of FDM 3D printing and traditional pharmaceutical technology, which are suitable for a patient's individual medication and chronopathology. The tablets were designed and prepared with the commercial verapamil hydrochloride tablets as core inside and the fused deposition modelling (FDM) 3D-printed shell outside. Filaments composed of hydroxypropylmethyl cellulose (HPMC) and polyethylenglycol (PEG) 400 were prepared by hot melt extrusion (HME) and used for fabrication of the shell.

FDM 3D-Printed Sustained-Release Gastric-Floating Verapamil Hydrochloride Formulations with Cylinder, Capsule and Hemisphere Shapes, and Low Infill Percentage.

The aim of this work was to design and fabricate fused deposition modeling (FDM) 3D-printed sustained-release gastric-floating formulations with different shapes (cylinder, capsule and hemisphere) and infill percentages (0% and 15%), and to investigate the influence of shape and infill percentage on the properties of the printed formulations. Drug-loaded filaments containing HPMC, Soluplus and verapamil hydrochloride were prepared via hot-melt extrusion (HME) and then used to print the following gastric-floating formulations: cylinder-15, capsule-0, capsule-15, hemisphere-0 and hemisphere-15. The morphology of the filaments and the printed formulations were observed by scanning electron microscopy (SEM).

Commonly and Specifically Activated Defense Responses in Maize Disease Lesion Mimic Mutants Revealed by Integrated Transcriptomics and Metabolomics Analysis.

Disease lesion mimic (/) mutants display disease-like spontaneous lesions in the absence of pathogen infection, implying the constitutive activation of defense responses. However, the genetic and biochemical bases underlying the activated defense responses in those mutants remain largely unknown. Here, we performed integrated transcriptomics and metabolomics analysis on three typical maize mutants , , and with large, medium, and small lesion size, respectively, thereby dissecting the activated defense responses at the transcriptional and metabolomic level.

Small-Molecule Fms-like Tyrosine Kinase 3 Inhibitors: An Attractive and Efficient Method for the Treatment of Acute Myeloid Leukemia.

Fms-like tyrosine kinase 3 (FLT3) is an important member of the class III receptor tyrosine kinase (RTK) family, which is involved in the proliferation of hematopoietic cells and lymphocytes. In recent years, increasing evidence have demonstrated that the activation and mutation of FLT3 is closely implicated in the occurrence and development of acute myeloid leukemia (AML). The exploration of small-molecule inhibitors targeting FLT3 has aroused wide interest of pharmaceutical chemists and is expected to bring new hope for AML therapy.

Total synthesis, chemical modification and structure-activity relationship of bufadienolides.

Bufadienolides are a type of natural cardiac steroids and originally isolated from the Traditional Chinese Medicine Chan'Su, they have been used for the treatment of heart disease in traditional remedies as well as in modern medicinal therapy with potent anti-tumor activities. Due to their unique molecular structures with unsaturated six-membered lactones attached to the steroid core, bufadienolides have received great attention in the synthetic organic community. This review presents total synthetic efforts to some representative bufadienolides, chemical modification of bufadienolides will also be given to discuss their structure-activity relationship in anti-tumor.

MRI Detectable Polymer Microspheres Embedded With Magnetic Ferrite Nanoclusters For Embolization: In Vitro And In Vivo Evaluation.

Objective: The objective of this study was to develop magnetic embolic microspheres that could be visualized by clinical magnetic resonance imaging (MRI) scanners aiming to improve the efficiency and safety of embolotherapy.

Methods And Discussion: Magnetic ferrite nanoclusters (FNs) were synthesized with microwave-assisted solvothermal method, and their morphology, particle size, crystalline structure, magnetic properties as well as T relaxivity were characterized to confirm the feasibility of FNs as an MRI probe. Magnetic polymer microspheres (FNMs) were then produced by inverse suspension polymerization with FNs embedded inside.

Preparation and In vitro Evaluation of FDM 3D-Printed Ellipsoid-Shaped Gastric Floating Tablets with Low Infill Percentages.

The aim of the study is to investigate the feasibility of fabricating FDM 3D-printed gastric floating tablets with low infill percentages and the effect of infill percentage on the properties of gastric floating tablets in vitro. Propranolol hydrochloride was selected as a model drug, and drug-loaded polyvinyl alcohol (PVA) filaments were produced by hot melt extrusion (HME). Ellipsoid-shaped gastric floating tablets with low infill percentage of 15% and 25% (namely E-15 and E-25) were then prepared respectively by feeding the extruded filaments to FDM 3D printer.

Design, synthesis and evaluation of 2-amino-imidazol-4-one derivatives as potent β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) inhibitors.

Inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) to prevent brain β-amyloid (Aβ) peptide's formation is a potential effective approach to treat Alzheimer's disease. In this report we described a structure-based optimization of a series of BACE1 inhibitors derived from an iminopyrimidinone scaffold W-41 (IC = 7.1 μM) by Wyeth, which had good selectivity and brain permeability but low activity.

Design, synthesis, and biological activity evaluation of BACE1 inhibitors with antioxidant activity.

The proteolytic enzyme β-secretase (BACE1) plays a central role in the synthesis of the pathogenic β-amyloid peptides (Aβ) in Alzheimer's disease (AD), antioxidants could attenuate the AD syndrome and prevent the disease progression. In this study, BACE1 inhibitors (D1-D18) with free radical-scavenging activities were synthesized by molecular hybridization of 2-aminopyridine with natural antioxidants. The biological activity evaluation showed that D1 had obvious inhibitory activity against BACE1, and strong antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS ) assay, which could be used as a lead compound for further study.

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction.

Herein we report a novel palladium-catalyzed reaction that results in phenanthrene derivatives using aryl iodides, -bromobenzoyl chlorides and norbornadiene in one pot. This dramatic transformation undergoes C-H activation, decarbonylation and subsequent a retro-Diels-Alder process. Pleasantly, this protocol has a wider substrate range, shorter reaction times and higher yields of products than previously reported methods.

Synthesis and Biological Evaluation of Scutellarein Alkyl Derivatives as Preventing Neurodegenerative Agents with Improved Lipid Soluble Properties.

Background: Exogenous antioxidants are considered as a promising therapeutic approach to treat neurodegenerative diseases since they could prevent and/or minimize the neuronal damage by oxidation.

Objective: Three series of lipophilic compounds structurally based on scutellarein (2), which is one metabolite of scutellarin (1) in vivo, have been designed and synthesized.

Methods: Their antioxidant activity was evaluated by detecting the 2-thiobarbituric acid reactive substance (TBARS) produced in the ferrous salt/ascorbate-induced autoxidation of lipids, which were present in microsomal membranes of rat hepatocytes.

Poly(acrylic acid) microspheres loaded with superparamagnetic iron oxide nanoparticles for transcatheter arterial embolization and MRI detectability: In vitro and in vivo evaluation.

To develop embolic microspheres with MRI detectability, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized and mixed with monomer of acrylic acid to prepare SPIONs-loaded polymerized microspheres (SPMs) by inverse suspension polymerization method. The SPMs were evaluated for the ability of embolization by investigating the morphology, particle size, elasticity and renal arterial embolization to rabbits. Meanwhile, the loading of SPIONs was verified by optical microscope, transmission electron microscope, Fourier transform infrared spectrum, vibrating sample magnetometer, X-ray diffraction and X-ray photoelectron spectroscopy, and the content of SPIONs in SPMs was measured quantitatively.

Preparation and In Vitro Evaluation of a MRI Contrast Agent Based on Aptamer-Modified Gadolinium-Loaded Liposomes for Tumor Targeting.

The aim of this study was to prepare aptamer-modified liposomes loaded with gadolinium (Gd) to enhance the effective diagnosis for tumor by MRI. A modified GBI-10 (GBI-10) was used to prepare targeted liposomes (GLs). Liposomes with GBI-10 aptamer (GLs) and without aptamer (non-targeted liposomes (NLs)) were also prepared as controls.

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging.

Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs).

Preparation and evaluation of biocompatible long-term radiopaque microspheres based on polyvinyl alcohol and lipiodol for embolization.

The aim of this work was to develop long-term radiopaque microspheres (LRMs) by entrapping lipiodol in biocompatible polyvinyl alcohol with multiple emulsions chemical crosslinking method. The high content of lipiodol (0.366 g/mL) was hardly released from LRMs in vitro and the radiopacity could maintain at least 3 months after subcutaneous injection in mice without weakening.

[Preparation and investigation of MRI-traceable Eudragit-E liquid embolic agent].

Objective: To develop and investigate the properties of MRI-traceable Eudragit-E liquid embolic agent (MR-E).

Methods: Polyethylene glycol-modified superparamagnetic iron oxides (PEG-SPIO) was synthesized by chemical co-precipitation method. MR-E was prepared by mixing PEG-SPIO and Eudragit-E liquid embolic agent homogeneously.

[Preparation and in vitro evaluation of crosslinked polyvinyl alcohol microspheres for embolization].

Objective: To develop and study the properties of crosslinked polyvinyl alcohol microspheres (PVA-Ms) for embolization.

Methods: The PVA-Ms were produced by emulsion chemical crosslinking method. Fourier transform infrared spectroscopy (FT-IR) was used to investigate the special functional groups of PVA-Ms; the morphology and particle size of PVA-Ms were determined by optical microscope; the ratio of water absorption and the swelling ratio were also investigated; the compressibility was examined by texture analyzer.

[Preparation and property study of doxorubicin loaded microspheres].

Objective: To prepare doxorubicin-loaded polyvinylalcohol-acrylic acid (PVA-AA) microspheres and evaluate properties of this chemoembolic agent.

Methods: PVA-AA microspheres were synthesized by inverse suspension polymerization method and then verified by infrared spectroscopy. drug loading (DL) and entrapment efficiency (EE%) were measured after doxorubicinwas loaded on PVA-AA microspheres.

Development and evaluation of liquid embolic agents based on liquid crystalline material of glyceryl monooleate.

New type of liquid embolic agents based on a liquid crystalline material of glyceryl monooleate (GMO) was developed and evaluated in this study. Ternary phase diagram of GMO, water and ethanol was constructed and three isotropic liquids (ILs, GMO:ethanol:water=49:21:30, 60:20:20 and 72:18:10 (w/w/w)) were selected as potential liquid embolic agents, which could spontaneously form viscous gel cast when contacting with water or physiological fluid. The ILs exhibited excellent microcatheter deliverability due to low viscosity, and were proved to successfully block the saline flow when performed in a device to simulate embolization in vitro.

Targeted hyperthermia after selective embolization with ferromagnetic nanoparticles in a VX2 rabbit liver tumor model.

Background: The purpose of this study was to observe the effect and feasibility of hyperthermia and the influence of heat on surrounding organs in a VX2 rabbit liver model exposed to an alternating magnetic field after embolization with ferromagnetic nanoparticles.

Methods: Forty rabbits containing implanted hepatic VX2 carcinomas were divided into four groups, each containing ten rabbits. Fourteen days after tumor transplantation, we opened the abdomen to observe the size and shape of the tumor.

Research of novel biocompatible radiopaque microcapsules for arterial embolization.

Embolic agents, such as microparticles, microspheres or beads used in current embolotherapy are mostly radiolucent, which means the agents are invisible under X-ray imaging during and after the process of embolization, and the fate of these particles cannot be precisely assessed. In this research, a radiopaque embolic agent was developed by encapsulating lipiodol in polyvinyl alcohol. The lipiodol-containing polyvinyl alcohol microcapsules (LPMs) were characterized and evaluated for their morphology, size distribution, lipiodol content, lipiodol release, elasticity, and deliverability through catheter.