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1.
Cell Biochem Biophys ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802601

RESUMO

The soluble-to-toxic transformation of intrinsically disordered amyloidogenic proteins such as amyloid beta (Aß), α-synuclein, mutant Huntingtin Protein (mHTT) and islet amyloid polypeptide (IAPP) among others are associated with disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Type 2 Diabetes (T2D), respectively. The dissolution of mature fibrils and toxic amyloidogenic intermediates, including oligomers, continues to be the pinnacle in the treatment of neurodegenerative disorders. Yet, methods to effectively and quantitatively report on the interconversion between amyloid monomers, oligomers and mature fibrils fall short. Here we describe a simplified method that implements the use of gel electrophoresis to address the transformation between soluble monomeric amyloid proteins and mature amyloid fibrils. The technique implements an optimized but well-known, simple, inexpensive, and quantitative assessment previously used to assess the oligomerization of amyloid monomers and subsequent amyloid fibrils. This method facilitates the screening of small molecules that disintegrate oligomers and fibrils into monomers, dimers, and trimers and/or retain amyloid proteins in their monomeric forms. Most importantly, our optimized method diminishes existing barriers associated with existing (alternative) techniques to evaluate fibril formation and intervention.

2.
Res Sq ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38585783

RESUMO

The soluble-to-toxic transformation of intrinsically disordered amyloidogenic proteins such as amyloid beta (Aß), α-synuclein, mutant Huntingtin Protein (mHTT) and islet amyloid polypeptide (IAPP) among others is associated with disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Type 2 Diabetes (T2D), respectively. The dissolution of mature fibrils and toxic amyloidogenic intermediates including oligomers continues to be the pinnacle in the treatment of neurodegenerative disorders. Yet, methods to effectively, and quantitatively, report on the interconversion between amyloid monomers, oligomers and mature fibrils fall short. Here we describe a simplified method that implements the use of gel electrophoresis to address the transformation between soluble monomeric amyloid proteins and mature amyloid fibrils. The technique implements an optimized but well-known, simple, inexpensive and quantitative assessment previously used to assess the oligomerization of amyloid monomers and subsequent amyloid fibrils. This method facilitates the screening of small molecules that disintegrate oligomers and fibrils into monomers, dimers, and trimers and/or retain amyloid proteins in their monomeric forms. Most importantly, our optimized method diminishes existing barriers associated with existing (alternative) techniques to evaluate fibril formation and intervention.

3.
Enzyme Microb Technol ; 174: 110377, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38147782

RESUMO

Xanthine is derived from hypoxanthine by xanthine oxidase (XOD), a flavoprotein containing molybdenum and non-haem iron, sulfur and from guanine by guanine deaminase enzyme. Xanthine is oxidized into uric acid by XOD. Xanthine is used as an indicator of fish freshness, based on the reactions in which ATP is degraded into xanthine and its quantity increases with time of fish death. Fresh fish meat is required in food industry for making high quality items. The determination of xanthine in biological fluids is also used in diagnosing and curing many diseases like renal failure, gout, xanthinuria, hyperuricemia. Various methods are available for detection of xanthine but most of them are complicated, time consuming less sensitive & specific and require expensive instrumental setup and trained person to operate. Enzyme based biosensors and non enzymic sensors overcome these disadvantages, as these are simple, rapid, specific, sensitive and easy to operate. Present review describes xanthine biosensors, which work optimally between pH 3.5-9.0, temperature 25 °C-65 °C, xanthine concentration ranging from 0.001-50 × 104 µM. These biosensors have also been used to measure xanthine concentration in beverages, urine and serum samples. Various modified electrodes have been discussed for the detection of xanthine using both enzymatic and non-enzymatic approaches in the present review.


Assuntos
Técnicas Biossensoriais , Xantina Oxidase , Humanos , Animais , Xantina , Hipoxantina , Xantina Oxidase/metabolismo , Técnicas Biossensoriais/métodos
4.
J Chem Phys ; 159(10)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37698194

RESUMO

The electrical conductivity of Na2O substituted zinc borate glasses has been studied in the frequency range of 10 mHz to 1 MHz and in the temperature range from 313 to 573 K. The conduction mechanism has been ascertained using the values of the frequency exponent (s) extracted from the fitting of experimental data of the real part of electric conductivity in light of the Almond-West equation. Depending on the glass composition, the ac conduction in the glasses happened via correlated barrier hopping and non-overlapping small polaron tunneling conduction models. The electric modulus studies support the assertion of composition dependent conduction mechanisms. Furthermore, electronic conduction and ionic conduction have been studied from impedance investigations. Equivalent circuit models were used to fit the Nyquist and Bode plots of each sample at the temperatures under consideration. It has been found that the activation energy values calculated from conductivity, electric modulus, and impedance measurements are more or less the same.

5.
Transplant Cell Ther ; 29(8): 530.e1-530.e5, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37192731

RESUMO

Hematopoietic cell transplantation (HCT) impacts recipients' quality of life (QoL). Few mindfulness-based interventions (MBI) in HCT recipients have shown feasibility, but heterogeneous practices and outcome measures have called into question the actual benefit. We hypothesized that self-guided isha kriya, a 12-minute guided meditation based on the principles of yoga focusing on breathing, awareness, and thought, as a mobile app would improve QoL in the acute HCT setting. This single-center, open-label, randomized controlled trial was conducted in 2021 to 2022. Autologous and allogeneic HCT recipients age ≥18 years were included. The study was approved by our Institutional Ethics Committee and registered at the Clinical Trial Registry of India, and all participants provided written informed consent. HCT recipients without access to smartphones or regular practitioners of yoga, meditation, or other mind-body practices were excluded. Participants were randomized to the control arm or the isha kriya arm at a 1:1 ratio stratified by type of transplantation. Patients in the isha kriya arm were instructed to perform the kriya twice daily from pre-HCT to day +30 post-HCT. The primary endpoint was QoL summary scores as assessed by the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) and the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) questionnaires. The secondary endpoints were the differences in QoL domain scores. The validated questionnaires were self-administered before the intervention and at days +30 and +100 post-HCT. The analysis of endpoints was done on an intention-to-treat basis. Domain and summary scores were calculated for each instrument as recommended by the developers. A P value < .05 was considered to indicate statistical significance, and Cohen's d effect size was used to determine clinical significance. A total of 72 HCT recipients were randomized to the isha kriya and control arms. Patients in the 2 arms were matched for age, sex, diagnosis, and type of HCT. The 2 arms showed no differences in pre-HCT QoL domain, summary, and global scores. At day +30 post-HCT, there was no difference between the arms in the mean FACT-BMT total score (112.9 ± 16.8 for the isha kriya arm versus 101.2 ± 13.9 for the control arm; P = .2) or the mean global health score (global mental health, 45.1 ± 8.6 versus 42.5 ± 7.2 [P = .5]; global physical health, 44.1 ± 6.3 versus 44.1 ± 8.3 [P = .4]) in the 2 groups. Similarly, there were no differences in physical, social, emotional, and functional domain scores. However, the mean bone marrow transplantation (BMT) subscale scores, which addresses BMT-specific QoL concerns, were statistically and clinically significantly higher in the isha kriya arm (27.9 ± 5.1 versus 24.4 ± 9.2; P = .03; Cohen's d = .5; medium effect size). This effect was transient; mean day +100 scores showed no difference (28.3 ± 5.9 versus 26.2 ± 9.4; P = .3). Our data indicate that the isha kriya intervention did not improve the FACT-BMT total and global health scores in the acute HCT setting. However, practicing isha kriya for 1 month was associated with transient improvement in the FACT-BMT subscale scores on day +30 but not on day +100 post-HCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Meditação , Yoga , Adolescente , Humanos , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida , Adulto , Masculino , Feminino
6.
Res Sq ; 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36945382

RESUMO

The soluble-to-toxic transformation of intrinsically disordered amyloidogenic proteins such as amyloid beta (Aß), α-synuclein, mutant Huntingtin Protein (mHTT) and islet amyloid polypeptide (IAPP) among others is associated with disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Type 2 Diabetes (T2D), respectively. Conversely, the dissolution of mature fibrils and toxic amyloidogenic intermediates including oligomers remains the holy grail in the treatment of neurodegenerative disorders. Yet, methods to effectively, and quantitatively, report on the interconversion between amyloid monomers, oligomers and mature fibrils fall short. For the first time, we describe the use of gel electrophoresis to address the transformation between soluble monomeric amyloid proteins and mature amyloid fibrils. The technique permits rapid, inexpensive and quantitative assessment of the fraction of amyloid monomers that form intermediates and mature fibrils. In addition, the method facilitates the screening of small molecules that disintegrate oligomers and fibrils into monomers or retain amyloid proteins in their monomeric forms. Importantly, our methodological advance diminishes major existing barriers associated with existing (alternative) techniques to evaluate fibril formation and intervention.

7.
Biosensors (Basel) ; 13(3)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36979598

RESUMO

An electrochemical biosensor was fabricated using nanoparticles of acetylcholinesterase (AChE) and choline oxidase (ChO)/Pt nanoparticles (PtNPs)/porous graphene oxide nanosheet (GONS) composite. A pencil graphite electrode (PGE) was used for the electrodeposition of nanocomposite and the determination of acetylcholine (ACh), a neurotransmitter. Various techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectra and cyclic voltammetry (CV) were used for characterization. This biosensor (AChENPs-ChONPs/GONS/PtNPs/PGE) indicated a very short response time (3 s), a lower limit of detection (0.001 µM), good linearity (0.001-200 µM), longer storage stability (6 months) and better reproducibility. The percent analytical recoveries of added acetylcholine in serum (5.0 and 10 µM) were found to be 97.6 ± 0.7 and 96.5 ± 0.3 for the present biosensor. The coefficients of variation were obtained to be 8% and 3.25%, correspondingly. The biosensor was applied to measure the ACh amount in the serum of healthy individuals and patients with Alzheimer's disease. The number of interferents had no effect on the biosensor at their physiological concentrations.


Assuntos
Técnicas Biossensoriais , Grafite , Nanopartículas Metálicas , Nanocompostos , Nanopartículas , Humanos , Acetilcolina , Acetilcolinesterase/química , Reprodutibilidade dos Testes , Enzimas Imobilizadas/química , Nanopartículas/química , Grafite/química , Técnicas Biossensoriais/métodos , Eletrodos , Nanopartículas Metálicas/química
8.
Biomater Adv ; 137: 212837, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35929242

RESUMO

The herbicide and viologen, N, N'-dimethyl-4,4'-bipyridinium dichloride (Paraquat) is known to be toxic to neuronal cells by a multifactorial process involving an elevation in the levels of reactive oxygen species (ROS), the triggering of amyloid-protein aggregation and their accumulation, collectively leading to neuronal dyshomeostasis. We demonstrate that green-chemistry-synthesized sustainable gelatin-derived carbon quantum dots (CQDs) mitigate paraquat-induced neurotoxic outcomes and resultant compromise in organismal mortality. Gelatin-derived CQDs were found to possess antioxidant properties and ameliorated ROS elevation in paraquat-insulted neuroblastoma-derived SHSY-5Y cells, protecting them from herbicide-induced cell death. These CQDs also increased lifespan in paraquat-compromised Caenorhabditis elegans and herbicide-mediated dopamine neuron ablation. Collectively, the data underscore the ability of this sustainably synthesized, environmentally friendly biocompatible nanomaterial to protect cell lines and organisms against neurotoxic outcomes. The study findings strategically position this relatively novel nanoscopic carbon quantum framework for further testing in vertebrate trials of neurotoxic insult.


Assuntos
Herbicidas , Síndromes Neurotóxicas , Pontos Quânticos , Carbono/farmacologia , Gelatina , Herbicidas/toxicidade , Humanos , Síndromes Neurotóxicas/etiologia , Paraquat/toxicidade , Pontos Quânticos/toxicidade , Espécies Reativas de Oxigênio
9.
ACS Chem Neurosci ; 13(16): 2399-2409, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35942850

RESUMO

The potent environmental herbicide and weedicide paraquat is linked to neuromotor defects and Parkinson's disease (PD). We have evaluated the neuroprotective role of citric acid-sourced carbon quantum dots (Cit-CQDs) on paraquat-insulted human neuroblastoma-derived SH-SY5Y cell lines and on a paraquat-exposed nematode (Caenorhabditis elegans). Our data reveal that Cit-CQDs are able to scavenge free radicals in test tube assays and mitigate paraquat-elevated reactive oxygen species (ROS) levels in SH-SY5Y cells. Furthermore, Cit-CQDs protect the cell line from paraquat, which otherwise elicits cell death. Cit-CQDs-challenged nematodes demonstrate enhanced survival rates 72 h post-paraquat exposure compared to controls. Paraquat ablates dopamine (DA) neurons, which results in compromised locomotor function in nematodes. However, the neurons remained intact when the nematodes were incubated with Cit-CQDs prior to neurotoxicant exposure. The collective data suggest Cit-CQDs offer neuroprotection for cell lines and organisms from xenotoxicant-associated neuronal injury and death. The study suggests Cit-CQDs as a potentially viable green chemistry-synthesized, biobased nanomaterial for intervention in neurodegenerative disorders.


Assuntos
Neuroblastoma , Pontos Quânticos , Carbono , Ácido Cítrico , Humanos , Neurônios , Paraquat/toxicidade
10.
Plants (Basel) ; 10(7)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34371629

RESUMO

A mineral fertiliser has positive effects in improving turmeric nutrients, soil enzymes and soil properties. The aim of this research was to study the effect of mineral fertilisers on the content of mineral elements in turmeric rhizome, soil enzymes activity and soil properties in the Tashkent Region, Uzbekistan. For the first time in Uzbekistan, the turmeric rhizome was cultivated to study the mineral elements present in the rhizome. A microplot experiment was conducted with four treatments including T1 (Control), T2 (N75P50K50 kg/ha), T3 (N125P100K100 kg/ha) and T4 (N100P75K75 + B3Zn6Fe6 kg/ha) and turmeric rhizome, which were collected for observation along with the soil samples. The analyses indicated that the NPK + BZnFe (100:75:75:3:6:6 kg/ha) treatment significantly improved minerals such as K, Ca, P, Mg and Na contents rhizome as compared to the control without fertiliser. Likewise, the maximum quantity of micronutrient content viz., Fe, Mn, Zn, Cu, Cr and Si was also recorded in turmeric rhizome treated with NPK + BZnFe (125:100:100:3:6:6 kg/ha). It showed an increase in these micronutrients in the rhizome compared to the control, followed by a low rate of NPK (75:50:50 kg/ha). The highest content in terms of total N, P, K content, humus, active phosphorus, potassium, and enzymes activity was also observed in soil with the treatment of mineral fertiliser viz., NPK + BznFe (100:75:75:3:6:6 kg/ha), which enhanced soil nutrient and enzyme activity. The NPK + BznFe (100:75:75:3:6:6 kg/ha) treatment significantly increased the active N content by 40%, total P content by 38% and total K content by 22% in comparison to the control without mineral fertiliser. Overall, it was found that NPK + BznFe (100:75:75:3:6:6 kg/ha) was significantly valuable for enhancing the total nitrogen, phosphorus, and potassium levels in the soil compared to control, which is useful for improving soil health in terms of soil enzyme and soil nutrients. Additionally, the micronutrients in turmeric rhizome were significantly enhanced when using this combination of fertiliser applications [NPK + BznFe (100:75:75:3:6:6 kg/ha)]. Therefore, this present study revealed that the NPK+BznFe (100:75:75:3:6:6 kg/ha) could produce the most significant yield of high-quality turmeric plants and improve soil properties in Uzbek soil-climate conditions.

11.
Plants (Basel) ; 10(6)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203887

RESUMO

Mung bean (Vigna radiata L.) sprout is a popular fresh vegetable, tasty and high in antioxidants. To increase yield and quality after the occurrence of both abiotic and biotic stresses, the application of seaweed extracts is of great importance. Hence, this study was conducted to determine the effect of Ascophyllum nodosum extract (ANE) in the presence of salt on the antioxidant potential of V. radiata sprouts. Different concentrations of ANE viz. 0.00, 0.01, 0.05, 0.10, and 0.50% and NaCl 0, 25, 50, 75, and 100 mM alone and in combinations were tested for researching the antioxidant potential of V. radiata sprouts at 0, 24, and 36 h of sprouting. The DPPH free-radical-scavenging activity of sprouts of V. radiata was found to increase with time and peaked at 24 h of treatment. The A. nodosum extract (0.01%) could reverse the ill effect of the low level of salinity posed by up to 25 mM NaCl. The increasing salinity deteriorated the antioxidant activity using ABTS method of sprouts down to 20.45% of the control at 100 mM NaCl. The total phenolic content (TPC), total flavonoid content (TFC), and reducing power of V. radiata sprouts was found to increase till 36 h of sprouting. A slight increase in TPC, TFC and reducing power was observed when seeds were treated with low concentrations of ANE. The elevation in TPC, TFC and reducing power upon treatment with low concentrations of ANE was also noticed in sprouts in saline combinations. Alpha amylase inhibition activity was found to reach a (67.16% ± 0.9) maximum at 24 h of sprouting at a 0.01% concentration of ANE. Tyrosinase inhibition and alpha glucosidase inhibition was 88.0% ± 2.11 and 84.92% ± 1.2 at 36 h of sprouting, respectively, at 0.01% concentration of ANE. A. nodosum extract is natural, environmentally friendly, and safe, and could be used as one of the strategies to decline stress at a low level and enhance the antioxidant activities in V. radiata sprouts, thus increasing its potential to be developed as an antioxidant-based functional food.

12.
ACS Appl Nano Mater ; 4(3): 2423-2433, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33969279

RESUMO

Prion-like amyloids self-template and form toxic oligomers, protofibrils, and fibrils from their soluble monomers; a phenomenon that has been implicated in the onset and progress of neurodegenerative disorders such as Alzheimer's (AD), Parkinson's (PD), Huntington's, and systemic lysozyme amyloidosis. Carbon quantum dots (CQDs), sourced from Na-citrate as a carbon precursor were synthesized and characterized before being tested for their ability to intervene in amyloidogenic (fibril-forming) trajectories. Hen-egg white lysozyme (HEWL) served as a model amyloidogenic protein. A pulse-chase lysozyme fibril-forming assay developed to examine the impact of CQDs on the HEWL amyloid-fibril-forming trajectory used ThT fluorescence as a reporter of mature fibril presence. The results revealed that the Na-citrate-derived CQDs were able to intervene at multiple points along the fibril-forming trajectory by preventing the conversion of both monomeric and oligomeric HEWL intermediates into mature fibrils. In addition, and importantly, the carbon nano material (CNM) was able to dissolve oligomeric HEWL into monomeric HEWL and provoke the disaggregation of mature HEWL fibrils. These results suggest that Na-citrate CQD's intervene in amyloidogenesis by multiple mechanisms. The gathered data, coupled with cell-line results demonstrating the relatively low cytotoxicity of Na-citrate CQDs, suggest that this emerging CNM has the potential to intervene both prophylactically and therapeutically in protein misfolding diseases. The aforementioned findings are likely to enable Na-citrate CQDs to eventually transition to both cell-line and preclinical models of protein-misfolding-related disorders. Importantly, the study outcomes positions Na-citrate CQDs as an important class of chemical, nanotechnological, and biobased interventional tools in neuroscience.

13.
Biomater Sci ; 9(3): 626-644, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33241797

RESUMO

Carbon nano onions (CNOs) are carbonaceous nanostructures composed of multiple concentric shells of fullerenes. These cage-within-cage structures remain as one of the most exciting and fascinating carbon forms, along with graphene and its derivatives, due to their unique chemical and physical properties. Their exceptional biocompatibility and biosafety make them an attractive choice in a wide range of areas, including biological systems. This nanomaterial displays low toxicity, high dispersity in aqueous solutions (upon surface functionalization), and high pharmaceutical efficiency. Even though CNOs were discovered almost simultaneously along with carbon nanotubes (CNTs), their potential in biomedical applications still appears unrealized. The existence of CNOs is equally important, just like any other carbon nanostructures such as CNTs and fullerenes, because they display the ability of carbon to form another unique nanostructure with wonderful properties. Therefore, this mini-review summarizes recent studies geared towards developing CNOs for various biomedical applications, including sensing, drug delivery, imaging, tissue engineering, and as a therapeutic drug. It concludes by discussing other potential applications of this unique nanomaterial.


Assuntos
Fulerenos , Nanoestruturas , Nanotubos de Carbono , Cebolas , Engenharia Tecidual
14.
Int J Biol Macromol ; 165(Pt A): 1455-1462, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33011265

RESUMO

An improved cytochrome c (Cyt c) biosensor based on immobilization of cytochrome c oxidase (COx) on the surface of graphene oxide nanoparticles (GONPs) electrodeposited onto pencil graphite (PG) electrode. Characterization of graphene oxide nanoparticle was done by Transmission electron microscopy (TEM), Fourier transform infra-red spectroscopy (FTIR) and X-ray diffraction study (XRD). The working electrode (COx/GONPs/PG) was characterized at its different stages of fabrication by scanning electron microscopy (SEM) and FTIR. Fabrication of Cyt c biosensor was done by connecting COx/GONPs/PG as working electrode, Ag/AgCl as reference electrode and Pt as auxiliary electrode to potentiostat. The mechanism of detection of present biosensor was based on oxidation of Cyt c (reduced) to Cyt c (oxidized) by COx resulting in flow of electrons through GONPs to the PG electrode, hence current generated is proportional to the concentration of Cyt c. Present biosensor exhibited optimum potential at 0.49 V with optimum pH 7.5 and optimum temperature 35°C. Biosensor showed linearity within 40-180 ng/ml having 40 ng/ml limit of detection. The precision i.e. within and between-batch coefficients of variation (CVs) were found <0.04% and <0.21% respectively. The enzyme electrode lost 50% of its initial activity when operated for more than 6 months on weekly basis. It was applied for detection of Cyt c level in in apparently healthy and diseased human sera. The present biosensing method was co-related with standard colorimetric method and co-relation coefficient was found 0.99.


Assuntos
Técnicas Biossensoriais , Citocromos c/isolamento & purificação , Grafite/química , Nanopartículas Metálicas/química , Citocromos c/química , Técnicas Eletroquímicas , Enzimas Imobilizadas/química , Humanos , Limite de Detecção
15.
Biomater Sci ; 8(15): 4109-4128, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32638706

RESUMO

With an aging population that has been increasing in recent years, the need for the development of therapeutic approaches for treatment of neurodegenerative disorders (ND) has increased. ND, which are characterized by the progressive loss of the structure or function of neurons, are often associated with neuronal death. In spite of screening numerous drugs, currently there is no specific treatment that can cure these diseases or slow down their progression. Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Huntington's disease, and prion diseases belong to ND which affect enormous numbers of people globally. There are some main possible reasons for failure in the treatment of neurodegenerative diseases such as limitations introduced by the Blood-Brain Barrier (BBB), the Blood-Cerebrospinal Fluid Barrier (BCFB) and P-glycoproteins. Current advances in nanotechnology present opportunities to overcome the mentioned limitations by using nanotechnology and designing nanomaterials improving the delivery of active drug candidates. Some of the basic and developing strategies to overcome drug delivery impediments are the local delivery of drugs, receptor-mediated transcytosis, physicochemical disruption of the BBB, cell-penetrating peptides and magnetic disruption. Recently, the application of nanoparticles has been developed to improve the efficiency of drug delivery. Nanoengineered particles as nanodrugs possess the capacity to cross the BBB and also show decreased invasiveness. Examples include inorganic, magnetic, polymeric and carbonic nanoparticles that have been developed to improve drug delivery efficiency. Despite numerous papers published in this filed, there are some unsolved issues that need to be addressed for successful treatment of neurodegenerative diseases. These are discussed herein.


Assuntos
Nanopartículas , Doenças Neurodegenerativas , Idoso , Barreira Hematoencefálica , Sistemas de Liberação de Medicamentos , Humanos , Nanotecnologia , Doenças Neurodegenerativas/tratamento farmacológico
16.
ACS Omega ; 5(22): 12583-12595, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32548442

RESUMO

The design of a drug that successfully overcomes the constraints imposed by the blood-brain barrier (BBB, which acts as a gatekeeper to the entry of substances into the brain) requires an understanding of the biological firewall. It is also of utmost importance to understand the physicochemical properties of the said drug and how it engages the BBB to avoid undesired side effects. Since fewer than 5% of the tested molecules can pass through the BBB, drug development pertaining to brain-related disorders takes inordinately long to develop. Furthermore, in most cases it is also unsuccessful for allied reasons. Several drug delivery systems (DDSs) have shown excellent potential in drug delivery across the BBB while demonstrating minimal side effects. This mini-review summarizes key features of the BBB, recapitulates recent advances in our understanding of the BBB, and highlights existing strategies for the delivery of drug to the brain parenchyma.

17.
ACS Appl Mater Interfaces ; 12(16): 18964-18977, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32216327

RESUMO

Antioxidants derived from nature, such as ellagic acid (EA), demonstrated high potency to mitigate neuronal oxidative stress and related pathologies, including Parkinson's disease. However, the application of EA is limited due to its toxicity at moderate doses and poor solubility, cellular permeability, and bioavailability. Here, we introduce a sustainably resourced, green nanoencasement strategy to overcome the limitations of EA and derive synergistic effects to prevent oxidative stress in neuronal cells. Chitosan, with its high biocompatibility, potential antioxidant properties, and flexible surface chemistry, was chosen as the primary component of the nanoencasement in which EA is immobilized. Using a rotenone model to mimic intracellular oxidative stress, we examined the effectiveness of EA and chitosan to limit cell death. Our studies indicate a synergistic effect between EA and chitosan in mitigating rotenone-induced reactive oxygen species death. Our analysis suggests that chitosan encapsulation of EA reduces the inherent cytotoxicity of the polyphenol (a known anticancer molecule). Furthermore, its encapsulation permits its delivery via a rapid burst phase and a relatively slow phase making the nanohybrid suitable for drug release over extended time periods.


Assuntos
Antioxidantes , Ácido Elágico , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Rotenona/toxicidade , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Quitosana/química , Ácido Elágico/química , Ácido Elágico/farmacocinética , Ácido Elágico/farmacologia , Humanos , Doença de Parkinson
18.
Mater Sci Eng C Mater Biol Appl ; 103: 109834, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349516

RESUMO

Bioactive polymers are highly used polymers for preparing electrospun nanofiber based scaffold in the field of wound dressing to treat chronic non-healing wounds. Here, we report, the fabrication and evaluation of Carica papaya incorporated poly (vinyl) alcohol (PVA) blended gelatin nanofibers. PVA/Gelatin/Carica papaya nanofibrous scaffold was fabricated by electrospinning method. The obtained nanofibrous scaffold was characterized by using various analytical techniques such as FTIR, XRD, TEM, FESEM, AFM, and TGA. The average diameter of these nanofibers was found in the range 140-160 nm using FESEM. This scaffold showed excellent antibacterial activity against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria. The hemocompatibility was analyzed using platelet adhesion test. The cytotoxic activity of these nanofibrous scaffold against fibroblast cells (NIH 3T3) was studied and found no cytotoxic effect. Therefore, these results substantiated that Carica papaya loaded PVA/Gelatin nanofibrous scaffold could be a promising candidate for wound healing application.


Assuntos
Antibacterianos/química , Bandagens , Carica/química , Gelatina/química , Nanofibras/química , Álcool de Polivinil/química , Cicatrização , Animais , Escherichia coli/crescimento & desenvolvimento , Humanos , Camundongos , Células NIH 3T3 , Staphylococcus aureus/crescimento & desenvolvimento
19.
Materials (Basel) ; 12(7)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30978909

RESUMO

The aim of the present investigation was to study the anti-oxidant effect of chitosan nanoparticles on a human SH-SY5Y neuroblastoma cell line using a rotenone model to generate reactive oxygen species. Chitosan nanoparticles were synthesized using an ionotropic gelation method. The obtained nanoparticles were characterized using various analytical techniques such as Dynamic Light Scattering, Scanning Electron Microscopy, Transmission Electron Microscopy, Fourier Transmission Infrared spectroscopy and Atomic Force Microscopy. Incubation of SH-SY5Y cells with 50 µM rotenone resulted in 35-50% cell death within 24 h of incubation time. Annexin V/Propidium iodide dual staining verified that the majority of neuronal cell death occurred via the apoptotic pathway. The incubation of cells with chitosan nanoparticles reduced rotenone-initiated cytotoxicity and apoptotic cell death. Given that rotenone insult to cells causes oxidative stress, our results suggest that Chitosan nanoparticles have antioxidant and anti-apoptotic properties. Chitosan can not only serve as a novel therapeutic drug in the near future but also as a carrier for combo-therapy.

20.
Molecules ; 23(9)2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30150595

RESUMO

While pharmaceutical drugs have revolutionized human life, there are several features that limit their full potential. This review draws attention to some of the obstacles currently facing the use of chemotherapeutic drugs including low solubility, poor bioavailability and high drug dose. Overcoming these issues will further enhance the applicability and potential of current drugs. An emerging technology that is geared towards improving overall therapeutic efficiency resides in drug delivery systems including the use of polymeric nanoparticles which have found widespread use in cancer therapeutics. These polymeric nanoparticles can provide targeted drug delivery, increase the circulation time in the body, reduce the therapeutic indices with minimal side-effects, and accumulate in cells without activating the mononuclear phagocyte system (MPS). Given the inroads made in the field of nanodelivery systems for pharmaceutical applications, it is of interest to review and emphasize the importance of Polymeric nanocarrier system for drug delivery in chemotherapy.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos , Nanopartículas , Polímeros , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Materiais Biocompatíveis/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Nanoestruturas/química , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Polimerização , Polímeros/síntese química , Polímeros/química , Solventes
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