Enzyme replacement therapies: What is the best option?

Despite many beneficial outcomes of the conventional enzyme replacement therapy (ERT), several limitations such as the high-cost of the treatment and various inadvertent side effects including the occurrence of an immunological response against the infused enzyme and development of resistance to enzymes persist. These issues may limit the desired therapeutic outcomes of a majority of the lysosomal storage diseases (LSDs). Furthermore, the biodistribution of the recombinant enzymes into the target cells within the central nervous system (CNS), bone, cartilage, cornea, and heart still remain unresolved. All these shortcomings necessitate the development of more effective diagnosis and treatment modalities against LSDs. Taken all, maximizing the therapeutic response with minimal undesired side effects might be attainable by the development of targeted enzyme delivery systems (EDSs) as a promising alternative to the LSDs treatments, including different types of mucopolysaccharidoses (MPSs ) as well as Fabry, Krabbe, Gaucher and Pompe diseases

Effects of process variables on micromeritic properties and drug release of non-degradable microparticles

Introduction: The purpose of this investigation was to evaluate microencapsulated controlled release preparation of theophylline using Eudragit RS 100 as the retardant material with high entrapment efficiency. Methods: Microspheres were prepared by the emulsion-solvent evaporation method. A mixed solvent system consisting of methanol and acetone and light liquid paraffin as oily phase were chosen. Sucrose stearate was used as the surfactant to stabilize the emulsification process. The prepared microspheres were characterized by drug loading, Fourier-transform infrared spectroscopy (FTIR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release studies were performed at pH 1.2 and 7.4 aqueous medium. Results: Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release rate. The drug loading microparticle Eudragit RS100(1:6) showed 60-75% of entrapment and mean particle size 205.93-352.76 μm.The results showed that, an increase in the ratio of polymer: drug (F5, 6: 1) resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. Conclusion: The release of theophylline is influenced by the drug to polymer ratio and particle size. Drug release is controlled by diffusion and the best-fit release kinetic is Higuchi model. © 2011 by Tabriz University of Medical Sciences

Synthesis and characterization of two novel antibacterial dendritic methacrylate-based dental monomers

This study explores the synthesis and characterization of two novel antibacterial dendritic methacrylate-based dental monomers. For this purpose, two dendritic esters have been synthesized via condensation reaction and then reacted with methacryloyl chloride to afford methacrylate-end caped dendritic esters. These compounds are subsequently converted to quaternary ammonium fluoride monomers (QAFMs) with decyl substituted side chain to produce two novel antibacterial dendreticdental monomers. The chemical structures of synthesized samples have been characterized using Fourier transform infrared (FTIR) and proton nuclear magnetic resonance (1H NMR) spectroscopies.The obtained monomers can be used to replace 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropyl)-phenyl]propane (Bis-GMA) as the base monomer of universal resin-based dental composites in the presence of a diluting monomer (e.g.,triethyleneglycoldimethacrylate; TEGDMA), mainly due to their superior characteristics such as multifunctionalities as well as antibacterial activities

Indoleamine 2, 3-dioxygenase inhibitors in immunochemotherapy of breast cancer: challenges and opportunities

Trafficking of macromolecular immunotherapy agent into the tumor microenvironment (TME) is a challenging issue. In the TME, cancer cells exploit indoleamine 2, 3-dioxygenase (IDO), as a cytosolic enzyme that catalyzes the L-tryptophan (Trp) through the kynurenine (Kyn) pathway, which could negatively regulate the activity of T cells. Thus, Trp/Kyn pathway, can be targeted with novel treatment modalities such as IDO1 inhibitor to benefit patients with aggressive solid tumors

Therapeutic impacts of enzyme-responsive smart nanobiosystems

An important arena of the sophisticated nanosystems (NSs) is the combination of the responsive features of NSs with the biocatalytic properties of enzymes. The development of such smart drug delivery systems (DDSs) has seminal effectiveness in targeting, imaging, and monitoring of cancer. These NSs can exhibit site-specific delivery of the toxic cargo in response to the endogenous/exogenous stimuli. Enzyme responsive/targeted DDSs display enhanced accumulation of cargo molecules in the tumor microenvironment (TME) with a spatiotemporal controlled-release behavior. Based on the unique features of enzyme responsive/targeted DDSs, they offer incredible promise in overcoming some limitations of the currently used conventional DDSs. Taken all, targeting TME with the enzyme-responsive targeted DDSs may lead to versatile clinical outcomes in various malignancies

Gap Junctions: The Claymore for Cancerous Cells

Introduction: Gap junctions play an important role in the cell proliferation in mammalian cells as well as carcinogenesis. However, there are controversial issues about their role in cancer pathogenesis. This study was designed to evaluate genotoxicity and cytotoxicity of Carbenoxolone (CBX) as a prototype of inter-cellular gap junction blocker in MCF7 and BT20 human breast cancer cells. Methods: The MCF7and BT20 human breast cancer cell lines were cultivated, and treated at designated confluency with different doses of CBX. Cellular cytotoxicity was examined using standard colorimetric assay associated with cell viability tests. Gene expression evaluation was carried out using real time polymerase chain reaction (PCR). Results: MCF7 and BT20 cells were significantly affected by CBX in a dose dependent manner in cell viability assays. Despite varying expression of genes, down regulation of pro- and anti-apoptotic genes was observed in these cells. Conclusion: Based upon this investigation, it can be concluded that CBX could affect both low and high proliferative types of breast cancer cell lines and disproportionate down regulation of both pre- and anti-apoptotic genes may be related to interacting biomolecules, perhaps via gap junctions