Biosusceptometria AC e nanopartículas magnéticas para avaliação de parâmetros biofísicos: renais, cerebrais e efeito corona
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Data
2019-02-26
Autores
Próspero, André Gonçalves [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A proposta deste trabalho é inédita e consiste na aplicação do sistema de Biosusceptometria AC (BAC), associado à nanopartículas magnéticas (MNPs), a fim de disponibilizar uma nova ferramenta para estudos de função e fisiologia renal, cerebral e efeito corona. Foram realizados experimentos com ratos para o estudo de parâmetros biofísicos da dinâmica de perfusão de MNPs nos rins e cérebro, em situações normais e alteradas, bem como sua biodistribuição no organismo. Além disso empregamos o sistema BAC para avaliar as alterações em propriedades magnéticas e farmacocinéticas das MNPs quando em contato com fluidos biológicos (formação de corona proteica - CP). No estudo de perfusão e dinâmica renal estudamos diferentes fases de lesão renal induzida por doxorrubicina, utilizando o sistema BAC para detectar as MNPs em trânsito nos rins do animal, bem como sua biodistribuição. O trabalho referente à dinâmica de perfusão cerebral utilizou o fármaco manitol, um conhecido disruptor hiperosmótico, para influenciar no fluxo sanguíneo cerebral e permeabilidade da barreira hematoencefálica. Assim, foi possível estudar as alterações que este fármaco causa no cérebro, contribuindo para o desenvolvimento de novas estratégias de diagnóstico e tratamento envolvendo este órgão. Estudamos também a formação da CP nas MNPs, seus impactos em propriedades magnéticas e farmacocinéticas das MNPs. Este trabalho mostra que esses parâmetros são relacionados, uma vez que as MNPs com menor formação de CP apresentam menores alterações nas propriedades magnéticas das MNPs e maiores tempos de circulação. Este trabalho contempla a aplicação de instrumentação física de baixo custo que subsidia aplicações na pesquisa do sistema renal e cerebral em modelos animais, além de novas aplicações de materiais nano estruturados em angiologia, nefrologia e neurologia, o que proporcionará futuras inovações em instrumentação biomédica, farmacologia, ciência biomédica, nanomedicina e fisiologia.
This work consists in the application of the AC Biosusceptometry (ACB) system, associated with magnetic nanoparticles (MNPs), to provide a new tool for studies of renal and cerebral function and physiology, and corona effect as well. We performed experiments using rats to study biophysical parameters of the MNPs perfusion dynamics in the kidneys and brain, in normal and altered situations, as well as their biodistribution in the animals’ body. Also, we applied the ACB system to evaluate changes in the MNPs magnetic and pharmacokinetic properties when in contact with biological fluids (corona protein formation - CP). In the renal perfusion dynamics studies, we accessed three phases of doxorubicin-induced kidney injury, using the ACB system to detect the transit of the MNPs in the animals’ kidneys, as well as its biodistribution. In work regarding the dynamics of cerebral perfusion, we used the drug mannitol, a known hyperosmotic disruptor, to influence the cerebral blood flow and permeability of the blood-brain barrier. It was possible to study the changes that this drug causes in the brain, contributing to the development of new strategies for cerebral diagnosis and treatment using nanomedicines. We also studied the CP formation in MNPs, its impacts on the magnetic and pharmacokinetic properties of MNPs. This work shows that these parameters are related, since, the MNPs with lower CP formation, presented smaller differences in the magnetic properties of the MNPs and the greater circulation times. This work was carried out with the objective of conducting applications of physics instrumentation on the renal and cerebral systems in animals, as well as new applications of nanomaterials in angiology, nephrology, and neurology, which gives innovative perspectives in biomedical instrumentation, pharmacology, biomedical science, nanomedicine, and physiology.
This work consists in the application of the AC Biosusceptometry (ACB) system, associated with magnetic nanoparticles (MNPs), to provide a new tool for studies of renal and cerebral function and physiology, and corona effect as well. We performed experiments using rats to study biophysical parameters of the MNPs perfusion dynamics in the kidneys and brain, in normal and altered situations, as well as their biodistribution in the animals’ body. Also, we applied the ACB system to evaluate changes in the MNPs magnetic and pharmacokinetic properties when in contact with biological fluids (corona protein formation - CP). In the renal perfusion dynamics studies, we accessed three phases of doxorubicin-induced kidney injury, using the ACB system to detect the transit of the MNPs in the animals’ kidneys, as well as its biodistribution. In work regarding the dynamics of cerebral perfusion, we used the drug mannitol, a known hyperosmotic disruptor, to influence the cerebral blood flow and permeability of the blood-brain barrier. It was possible to study the changes that this drug causes in the brain, contributing to the development of new strategies for cerebral diagnosis and treatment using nanomedicines. We also studied the CP formation in MNPs, its impacts on the magnetic and pharmacokinetic properties of MNPs. This work shows that these parameters are related, since, the MNPs with lower CP formation, presented smaller differences in the magnetic properties of the MNPs and the greater circulation times. This work was carried out with the objective of conducting applications of physics instrumentation on the renal and cerebral systems in animals, as well as new applications of nanomaterials in angiology, nephrology, and neurology, which gives innovative perspectives in biomedical instrumentation, pharmacology, biomedical science, nanomedicine, and physiology.
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Palavras-chave
biofísica cerebral, biofísica renal, Biosusceptometria de corrente alternada, efeito corona, Nanopartículas magnéticas