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Enzyme Kinetics and Drugs as Enzyme Inhibitors
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Sonowal et al. (2017) found a way to use DOX for the treatment of CRC; they could show that the additional administration of the aldose reductase inhibitor Fidarestat (see scheme on the previous page) limits the cardiotoxicity of DOX by decreasing the growth of CRC cells so that fidarestat, as an adjuvant drug in combination with DOX, allows a reduction of the dose of the latter. Furthermore, aldose reductase inhibition significantly reduces angiogenesis in vivo and in vitro as reported earlier by the same group (Tammali et al., 2011). A further finding was that Fidarestat decreases the expression of drug transporter proteins such as multidrug resistance protein 1, multidrug resistance-associated protein, or ATP-binding cassette (ABC) transporters (Borst et al.,. 2000; Choi, 2005; Li et al., 2016). For epigenetic regulation of drug transporter expression in human tissues with consequences for an individualized drug therapy, see Hirota et al. (2017).
Development of Ophthalmic Formulations
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
Paramita Sarkar, Martin Coffey, Mohannad Shawer
Intraocular implants are usually placed intravitreally and at the pars plana of the eye and, therefore, require minor surgery. However, the use of implants has the benefit of bypassing the blood–ocular barriers to deliver constant therapeutic levels of drug at the site of action, avoidance of repeated administration, and use of smaller doses of drugs [76]. Implants may be nonbiodegradable or biodegradable depending on the material from which they are fabricated. Biodegradable implants of a poly (dl-lactic-co-glycolic acid) implant containing a novel aldose reductase inhibitor, fabricated with 50% drug loading, have been shown to give a sustained drug release in vitro and in vivo in rats [77]. Nonbiodegradable implants provide more accurate/reproducible dosing lasting over longer periods of time than biodegradable inserts [64]. The nonbiodegradable implants, however, require surgical removal after completion of therapy. Vitrasert® and Retisert® (Bausch and Lomb) are two clinically used nonbiodegradable implants for the treatment of cytomegalovirus or CMV retinitis (Acquired Immuno Deficiency Syndrome or AIDS related) and chronic uveitis, respectively. Other implant systems in different phases of clinical trials include Medidur® (Alimera Sciences) for the treatment of diabetic macular edema, and Surodex® and Posurdex® (Allergan, USA) containing dexamethasone.
Picometer Detection by Adaptive Holographic Interferometry
Published in Klaus D. Sattler, Fundamentals of PICOSCIENCE, 2013
Howard, E. I., Sanishvili, R., Cachau, R. E., Mitschler, A., Chevrier, B., Barth, P., Lamour, V. et al. 2004. Ultra-high resolution drug design I: Details of interactions in human aldose reductase-inhibitor complex at 0.66Å. Proteins: Struct. Funct. Genet. 55:792-804.
Bio-medical potential of chalcone derivatives and their metal complexes as antidiabetic agents: a review
Published in Journal of Coordination Chemistry, 2021
Since aldose reductase exhibits a high value of Michaelis constant (Km) for glucose, it comes into action only during the hyperglycemic conditions. In the next step, sorbitol dehydrogenase oxidizes the sorbitol to fructose using NADP+ [60]. But cells have less sorbitol dehydrogenase compared to aldose reductase except liver and seminal vesicle tissues. So because of low expression of sorbitol dehydrogenase, sorbitol starts accumulating inside the cells. Since it is osmotically active, it invites water inside the cells causing swelling. This swelling of cells alters its functioning such as opacity of lens (cataract formation), polyneuropathy caused by the dysfunction of neural cells and renal tuberculosis [61]. So, aldose reductase inhibitors can avert secondary diabetic complications.