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In Silico Studies on Pharmacokinetics and Neuroprotective Potential of 25Mg2+: Releasing Nanocationites - Background and Perspectivesстатья
- Авторы: Fursov Valentin V., Fursov Ilia V., Bukhvostov Alexander A., Majouga A.G., Kuznetsov Dmitry A.
- Сборник: Pharmacogenetics
- Год издания: 2021
- Место издания: IntechOpen
- DOI: 10.5772/intechopen.97729
- Аннотация: Sharp blood circulation disorders are known for their capability to promote such abundant and hardly treatable pathologies as myocardium infarction and the ischemic brain stroke (“insult”). Noteworthy, the stroke — related brain tissue metabolic damages involve an essential ATP deplete clash along with a suppression of brain specific nucleotide — associated kinases and ATP synthase, both Mg2+ — dependent complex enzyme “machineries”. This itself makes the latter’s a legitimate target for some advanced pharmaceuticals as long as the drug — induced overstimulation of corresponding enzymatic activity is the case. Thus, magnetic isotope effects (MIE) of the nuclear spin possessing paramagnetic 25Mg2+ ions might modulate the brain creatine kinase, alfa-glycerophosphate kinase and pyruvate kinase catalytic activities in a way of a remarkable ATP hyperproduction required to compensate the hypoxia caused acute metabolic breakdown. To realize the Magnesium-25 pharmacological potential, a low-toxic amphiphilic cationite nanoparticles were introduced lately. Particularly, the Magnesium — releasing porphyrin-fullerene nanoadduct (cyclohexyl-C60-porphyrin, PMC16) has been proposed to meet expectations dealing with a targeted delivery of 25Mg2+ towards the brain ischemia surrounding areas. In order to optimize a multi-step [25Mg2+]4PMC16 preclinical trial scenario, the In Silico algorithms are to be developed and analyzed. In this study, these algorithms are in a focus with a special emphasize on a novel combination of slightly modified Gompertzian equation systems and a non-Markov population dynamics concept. This In Silico approach takes into account some literature-available patterns of brain hypoxia pathogenesis, the resulted simulation model could be considered as a promising tool for further research on experimental nanopharmacology of the ischemic stroke.
- Добавил в систему: Бачева Анна Владимировна