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Design of Bioresponsive Polymers
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Anita Patel, Jayvadan K. Patel, Deepa H. Patel
Naturally, bacteria mostly to be found in the colon generate particular enzymes, counting reductive enzymes like azoreductase or else hydrolytic enzymes like glycosidases which have the capability to degrade a variety of polysaccharides, for example, amylase/amylopectin, CS, cyclodextrin, dextrin, and pectin [115–117]. The polysaccharide dextran can be degraded by the microbial enzyme dextranase which developed by preparing hydrogels crosslinked with diisocyanate [118]. Enzymes are employed to demolish the polymer or its assemblies in the majority enzyme-responsive polymer systems and also these polymers do not necessitate an external stimulus for their breakdown, show high selectivity, and able to work in mild conditions. As an instance, polymer systems on the basis of alginate/CS or DEXS/CS microcapsules are reactive to chitosanase [119] and azoaromatic bonds are responsive to azoreductase [120]. To generate pH-responsive hydrogels azoaromatic bonds were employed as crosslinking agents owing to acidic co-monomers. As a result of the ionization of carboxylic acid groups, the hydrogels swell while passing through the GIT. Azoreductase can way in the cross-links of the swollen hydrogels and debase the matrix to release the protein drugs in the colon.
Mechanisms of action
Published in Fazal-I-Akbar Danish, Ahmed Ehsan Rabbani, Pharmacology in 7 Days for Medical Students, 2018
Fazal-I-Akbar Danish, Ahmed Ehsan Rabbani
α-glucosidase inhibitors are competitive inhibitors of membrane-bound α-glucosidases (sucrase, maltase, glycoamylase, dextranase) in the intestinal brush border. α-glucosidases cause hydrolysis of oligosaccharides to glucose and other sugars. By inhibiting this enzyme, these drugs delay the digestion and thus absorption of ingested starch and disaccharides thus avoiding postprandial hyperglycemia. In fact post-prandial glycemic excursions are lowered by as much as 45–60 mg/dl. Thus the need of increased post-prandial release of insulin to control postprandial hyperglycemia is lowered by these drugs – an insulin-sparing effect.
Superparamagnetic Contrast Agents
Published in Michel M. J. Modo, Jeff W. M. Bulte, Molecular and Cellular MR Imaging, 2007
Claire Corot, Marc Port, Irène Guilbert, Philippe Robert, Jean-Sebastien Raynaud, Caroline Robic, Jean-Sebastien Raynaud, Philippe Prigent, Anne Dencausse, Idée Jean-Marc
Dextran-coated iron oxide nanoparticles are biodegradable, and therefore do not have any long-term toxicity: intracellular dextranase cleaves the dextran moiety and iron oxide is solubilized into iron ions, which are progressively incorporated into the hemoglobin pool.3 Van Beers et al.85 showed that the distribution of ferumoxtran-10 in the liver is fairly complex, as it can be located in both the vascular and interstitial spaces as well as inside cells. The predominant site of uptake is Kupffer cells; negligible uptake is observed experimentally in hepatocytes only at very high dose levels. The highest concentrations per gram of tissue, much higher than those observed in the liver, are found in the spleen and lymph nodes. The distribution and elimination data obtained with 14C-ferumoxtran-10 are investigated, in comparison with 59Fe data, to understand the metabolism of nanoparticles. In view of the differences between the outcome of 59Fe- and 14C-linked radioactivities, the dextran coating appears to undergo progressive degradation after uptake by macrophages and is almost exclusively eliminated in the urine (89% in 56 days) due to the low molecular weight of the dextran used. The remaining dextran is excreted in the feces. The iron contained in ferumoxtran-10 is incorporated into the body’s iron store and is progressively found in the red blood cells (hemoglobin). Like endogenous iron, it is eliminated very slowly, as only 16 to 21% of the iron injected is eliminated after 84 days in the feces (negligible urinary excretion < 1%). The same behavior has been described for ferumoxides. The degradation of iron oxide has been described to occur in the lysosomes of macrophages. Similar rates of erythrocyte incorporation of iron have been reported for radiolabeled ferritin.86
Orally delivered targeted nanotherapeutics for the treatment of colorectal cancer
Published in Expert Opinion on Drug Delivery, 2020
Xueqing Zhang, Heliang Song, Brandon S.B. Canup, Bo Xiao
Solid lipid NPs (SLNs) are also made from lipids, which are stable in a biological system due to their solid core structures. Very recently, Shen et al. constructed DOX and superparamagnetic iron oxide NPs-loaded SLNs, and further functionalized their surfaces with folate (FA) and dextran. The dextran shells can prevent SLNs from adsorption in upper GIT and can be subsequently degraded by dextranase in the colon, resulting in the exposure of FA moieties. The exposed FA molecules would then facilitate the specific cellular uptake by colon cancer cells through FA receptor-mediated endocytosis. The animal experiments demonstrated that these hierarchically targetable SLNs could effectively inhibit the primary CRC tumors and the peritoneal metastasis via oral route [28].
Regulatory mechanisms of exopolysaccharide synthesis and biofilm formation in Streptococcus mutans
Published in Journal of Oral Microbiology, 2023
Ting Zheng, Meiling Jing, Tao Gong, Jiangchuan Yan, Xiaowan Wang, Mai Xu, Xuedong Zhou, Jumei Zeng, Yuqing Li
Dextranase (Dex) is a glucanase involved in the degradation of water-soluble glucans, and includes DexA and DexB [83]. DexA breaks the α−1,6-linkage of the extracellular glucans to produce oligosaccharides, which are degraded into monosaccharides by DexB glucosidase after entering the cells [84–86]. Yang et al. revealed that dexA knockout results in an increased transcription of genes related to exopolysaccharides synthesis, including gtfB, gtfD and ftf [87]. In addition, the biofilms of the strains overexpressing dexA lack exopolysaccharides matrix and are unable to aggregate into dense and continuous microcolonies [87]. These results indicate an important role of the dexA gene in the formation of S. mutans biofilm.
Advancement in nanotechnology-based approaches for the treatment and diagnosis of hypercholesterolemia
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Nidhi Gupta, Nikita Sharma, Sandeep K. Mathur, Ramesh Chandra, Surendra Nimesh
With the advancement in research, there have been substantial developments in imaging and diagnostic techniques for the detection and identification of diseased state in vivo. Nanotechnology has enormous potential to increase the sensitivity, selectivity of the conventional diagnostic methods owing to its nanoscale size and large surface area. Nowadays, the nanomaterials have been designed to provide multiple functions, i.e. different components can be used for both the diagnostic as well as therapeutic approach. Several works has demonstrated that the nanoparticles assist in the improved quantitative estimation of lipid levels. In a study, lipoprotein profile has been analyzed through the use of gold nanoparticles conjugated with small, dense and low-density lipoprotein (sdLDL). It has been evident from the results that improved peak efficiency was obtained when gold nanoparticles (AuNPs) were added to the sample. The microchip-based capillary electrophoresis assays further provides lipoprotein profile and facilitates early detection of atherosclerotic diseases [56]. In addition, it has been observed that on intravenous administration, dextran-coated iron oxide nanoparticle gets accumulated in the inflamed lesions. Dextran receptor-mediated uptake resulted in an effective internalization of the formulated superparamagnetic nanoparticles. Dextran gets cleaved with the action of intracellular dextranase and iron oxide gets solubilized into iron ions preceded by the progressive accumulation at the ruptured area. An enhanced sensitivity and spatial resolution of the MRI imaging has been obtained, that further assists in mapping the atherosclerotic vascular area [57].