Amphiphilic Nanocarrier Systems for Curcumin Delivery in Neurodegenerative Disorders

Neurodegenerative diseases have become a major challenge for public health because of their incurable status. Soft nanotechnology provides potential for slowing down the progression of neurodegenerative disorders by using innovative formulations of neuroprotective antioxidants like curcumin, resveratrol, vitamin E, rosmarinic acid, 7,8-dihydroxyflavone, coenzyme Q10, and fish oil. Curcumin is a natural, liposoluble compound, which is of considerable interest for nanomedicine development in combination therapies. The neuroprotective effects of combination treatments can involve restorative mechanisms against oxidative stress, mitochondrial dysfunction, inflammation, and protein aggregation. Despite the anti-amyloid and anti-tau potential of curcumin and its neurogenesis-stimulating properties, the utilization of this antioxidant as a drug in neuroregenerative therapies has huge limitations due to its poor water solubility, physico-chemical instability, and low oral bioavailability. We highlight the developments of soft lipid- and polymer-based delivery carriers of curcumin, which help improve the drug solubility and stability. We specifically focus on amphiphilic liquid crystalline nanocarriers (cubosome, hexosome, spongosome, and liposome particles) for the encapsulation of curcumin with the purpose of halting the progressive neuronal loss in Alzheimer’s, Parkinson’s, and Huntington’s diseases and amyotrophic lateral sclerosis (ALS).

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Regulation of Brain Cholesterol: What Role Do Liver X Receptors Play in Neurodegenerative Diseases?

International Journal of Molecular Sciences ◽

10.3390/ijms20163858 ◽

2019 ◽

Vol 20 (16) ◽

pp. 3858 ◽

Cited By ~ 9

Author(s):

Kevin Mouzat ◽

Aleksandra Chudinova ◽

Anne Polge ◽

Jovana Kantar ◽

William Camu ◽

...

Keyword(s):

Neurodegenerative Disorders ◽

Target Genes ◽

Major Constituent ◽

Liver X Receptors ◽

Neuroprotective Effects ◽

Brain Cholesterol ◽

Pharmacological Targets ◽

The Central Nervous System ◽

X Receptors ◽

Lateral Sclerosis

Liver X Receptors (LXR) alpha and beta are two members of nuclear receptor superfamily documented as endogenous cholesterol sensors. Following conversion of cholesterol in oxysterol, both LXR isoforms detect intracellular concentrations and act as transcription factors to promote expression of target genes. Among their numerous physiological roles, they act as central cholesterol-lowering factors. In the central nervous system (CNS), cholesterol has been shown to be an essential determinant of brain function, particularly as a major constituent of myelin and membranes. In the brain, LXRs act as cholesterol central regulators, and, beyond this metabolic function, LXRs have additional roles such as providing neuroprotective effects and lowering neuroinflammation. In many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), and multiple sclerosis (MS), dysregulations of cholesterol and oxysterol have been reported. In this paper, we propose to focus on recent advances in the knowledge of the LXRs roles on brain cholesterol and oxysterol homeostasis, neuroinflammation, neuroprotection, and their putative involvement in neurodegenerative disorders. We will discuss their potential use as candidates for both molecular diagnosis and as promising pharmacological targets in the treatment of ALS, AD, or MS patients.

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Complexation with Hydroxypropyl-gama-Cyclodextrin of Birch Tree Extract Physico-chemical Characterisation of their Binary Products

Revista de Chimie ◽

10.37358/rc.08.6.1854 ◽

2008 ◽

Vol 59 (6) ◽

Cited By ~ 1

Author(s):

Codruta Soica ◽

Cristina A. Dehelean ◽

Valentin Ordodi ◽

Diana Antal ◽

Vicentiu Vlaia

Keyword(s):

Inclusion Complexes ◽

Water Solubility ◽

In Vitro Dissolution ◽

Molar Ratio ◽

Bark Extract ◽

Birch Bark ◽

Preparation Methods ◽

Birch Tree ◽

Physico Chemical

Birch bark contains important pentacyclic triterpens that determine an anticancer, anti-inflammatory and antiviral activity. The compounds can be extracted by simple procedures with organic solvents. The major problem of this type of triterpens is their low water solubility which can be increased by physical procedures like cyclodextrin complexation. The aim of present study was to analyse the products between birch bark extract and hydroxypropyl-g -cyclodextrin. Hydroxypropyl-g -cyclodextrin (HPGCD) was used as a host to improve its solubility in water, via inclusion complex formation. In order to obtain the inclusion complexes, 1:2 molar ratio and two preparation methods (physical mixing, kneading) were used. The inclusion complexes were analyzed by in vitro dissolution tests, thermal analysis and X-ray diffraction.

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Healthy Gut, Healthy Brain: The Gut Microbiome in Neurodegenerative Disorders

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200413091101 ◽

2020 ◽

Vol 20 (13) ◽

pp. 1142-1153 ◽

Cited By ~ 3

Author(s):

Sreyashi Chandra ◽

Md. Tanjim Alam ◽

Jhilik Dey ◽

Baby C. Pulikkaparambil Sasidharan ◽

Upasana Ray ◽

...

Keyword(s):

Gut Microbiota ◽

Neurodegenerative Disorders ◽

The Body ◽

Therapeutic Approaches ◽

Cns Disorders ◽

Physiological Conditions ◽

Pathological Conditions ◽

The Central Nervous System ◽

Present Understanding ◽

Lateral Sclerosis

Background: The central nervous system (CNS) known to regulate the physiological conditions of human body, also itself gets dynamically regulated by both the physiological as well as pathological conditions of the body. These conditions get changed quite often, and often involve changes introduced into the gut microbiota which, as studies are revealing, directly modulate the CNS via a crosstalk. This cross-talk between the gut microbiota and CNS, i.e., the gut-brain axis (GBA), plays a major role in the pathogenesis of many neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington’s disease (HD). Objective: We aim to discuss how gut microbiota, through GBA, regulate neurodegenerative disorders such as PD, AD, ALS, MS and HD. Methods: In this review, we have discussed the present understanding of the role played by the gut microbiota in neurodegenerative disorders and emphasized the probable therapeutic approaches being explored to treat them. Results: In the first part, we introduce the GBA and its relevance, followed by the changes occurring in the GBA during neurodegenerative disorders and then further discuss its role in the pathogenesis of these diseases. Finally, we discuss its applications in possible therapeutics of these diseases and the current research improvements being made to better investigate this interaction. Conclusion: We concluded that alterations in the intestinal microbiota modulate various activities that could potentially lead to CNS disorders through interactions via the GBA.

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Physico-Chemical Characteristics of Sapota (Chikoo) Powder based Value Added Pasta Product using Semolina (Suji) and Maida

Journal of AgriSearch ◽

10.21921/jas.v7i04.19394 ◽

2020 ◽

Vol 7 (04) ◽

Author(s):

SATYA NARAYAN SINGH ◽

RAJESH G BURBADE ◽

HITESH SANCHAVAT ◽

P S PANDIT

Keyword(s):

Bulk Density ◽

Crude Protein ◽

Water Solubility ◽

Value Added ◽

Absorption Capacity ◽

Oil Absorption ◽

Minimum Value ◽

Maximum Value ◽

Physico Chemical ◽

Specific Length

The cereals of today are more nutritious and healthful than ever before. Cereals processing is one of the oldest and the most essential part of all food technologies. Pasta products and noodles have been staple foods since ancient times in many countries all over the world. In this study pasta formulation was substituted with blending sapota powder in different proportions (4 levels i.e. 0%, 10%, 20%, 30%) into semolina and maida flour separately. Pasta products were prepared using eight different formulations and adding water (approximately 31% of total weight) in DOLLY pasta extruder machine. All the samples were evaluated for physical properties: specific length (mm/g), bulk density (kg/m3), specific density (kg/m3) and porosity (%); functional properties: water absorption index (%), water solubility index (%) and oil absorption capacity (ml/g) and nutritional compositions: moisture (%), crude protein (%), fat (%) and carbohydrate (%). Highest specific length 36.20 mm/g was observed for T5 treatment, low bulk density 368.10 kg/m3 was observed for T5 and highest porosity 9.24% was found for T1 treatment. The maximum WAI, WSI values 325.83%, 17.33% respectively was observed for T1 treatment and minimum value of oil absorption capacity 1.06 ml/g for T8 treatment. The moisture content of dried pasta products was found in the range of 6 to 7%. The maximum value of crude protein 13.07% was found for T5 and minimum value 8.81% for T4 treatments. The fat contents were varied from 1.02% to 1.28 %. The maximum value of carbohydrate was 76.20% for T1 and minimum value 65.41% for T8.

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An autopsy-proven case of Corticobasal degeneration heralded by Pontine infarction

BMC Neurology ◽

10.1186/s12883-021-02178-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dallah Yoo ◽

Sung-Hye Park ◽

Sungwook Yu ◽

Tae-Beom Ahn

Keyword(s):

Neurodegenerative Disorders ◽

Clinical Manifestations ◽

Neuronal Loss ◽

Corticobasal Degeneration ◽

Executive Dysfunction ◽

Lacunar Infarction ◽

Cortical Atrophy ◽

Dystonic Posturing ◽

Proven Case ◽

The Right

Abstract Background Neurodegenerative disorders are characterized by insidious progression with poorly-delineated long latent period. Antecedent clinical insult could rarely unmask latent neurodegenerative disorders. Here, we report an autopsy-proven case of corticobasal degeneration which was preceded by a lacunar infarction. Case presentation A 58-year-old man presented with acute ataxia associated with a lacunar infarction in the right paramedian pons. His ataxia persisted with additional progressive gait difficulty and left arm clumsiness. Six months later, a follow-up neurological examination showed asymmetrical bradykinesia, apraxia, dystonic posturing, postural instability, and mild ataxia of the left limbs. Cognitive examination revealed frontal executive dysfunction and visuospatial difficulties. Dopamine transporter imaging scan demonstrated bilateral reduced uptakes in mid-to-posterior putamen, more prominent on the right side. Levodopa-unresponsive parkinsonism, asymmetric limb dystonia, and ideomotor apraxia became more conspicuous, while limb ataxia gradually vanished. The patient became unable to walk without assistance after 1 year, and died 4 years after the symptom onset. Autopsy findings showed frontoparietal cortical atrophy, ballooned neurons, and phosphorylated tau-positive astrocytic plaques and neuropil threads with gliosis and neuronal loss, confirming the corticobasal degeneration. Conclusions The case illustrates that precedent clinical events such as stroke might tip a patient with subclinical CBS into overt clinical manifestations.

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Piroxicam Loading onto Mesoporous Silicas by Supercritical CO2 Impregnation

Molecules ◽

10.3390/molecules26092500 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2500

Author(s):

Marta Gallo ◽

Luca Serpella ◽

Federica Leone ◽

Luigi Manna ◽

Mauro Banchero ◽

...

Keyword(s):

Supercritical Co2 ◽

Water Solubility ◽

Solid Dispersions ◽

Mesoporous Silicas ◽

Incipient Wetness Impregnation ◽

Pore Blocking ◽

Physico Chemical ◽

Adsorption From Solution ◽

First Time ◽

Loading Procedure

Piroxicam (PRX) is a commonly prescribed nonsteroidal anti-inflammatory drug. Its efficacy, however, is partially limited by its low water solubility. In recent years, different studies have tackled this problem and have suggested delivering PRX through solid dispersions. All these strategies, however, involve the use of potentially harmful solvents for the loading procedure. Since piroxicam is soluble in supercritical CO2 (scCO2), the present study aims, for the first time, to adsorb PRX onto mesoporous silica using scCO2, which is known to be a safer and greener technique compared to the organic solvent-based ones. For comparison, PRX is also loaded by adsorption from solution and incipient wetness impregnation using ethanol as solvent. Two different commercial mesoporous silicas are used (SBA-15 and Grace Syloid® XDP), which differ in porosity order and surface silanol population. Physico-chemical analyses show that the most promising results are obtained through scCO2, which yields the amorphization of PRX, whereas some crystallization occurs in the case of adsorption from solution and IWI. The highest loading of PRX by scCO2 is obtained in SBA-15 (15 wt.%), where molecule distribution appears homogeneous, with very limited pore blocking.

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Benefits under the Sea: The Role of Marine Compounds in Neurodegenerative Disorders

Marine Drugs ◽

10.3390/md19010024 ◽

2021 ◽

Vol 19 (1) ◽

pp. 24

Author(s):

Mariano Catanesi ◽

Giulia Caioni ◽

Vanessa Castelli ◽

Elisabetta Benedetti ◽

Michele d’Angelo ◽

...

Keyword(s):

Oxidative Stress ◽

Neurodegenerative Disorders ◽

Extreme Temperature ◽

Bioactive Molecules ◽

Neuroprotective Effects ◽

Physical Conditions ◽

Adjuvant Therapies ◽

Marine Habitats ◽

Marine Compounds

Marine habitats offer a rich reservoir of new bioactive compounds with great pharmaceutical potential; the variety of these molecules is unique, and its production is favored by the chemical and physical conditions of the sea. It is known that marine organisms can synthesize bioactive molecules to survive from atypical environmental conditions, such as oxidative stress, photodynamic damage, and extreme temperature. Recent evidence proposed a beneficial role of these compounds for human health. In particular, xanthines, bryostatin, and 11-dehydrosinulariolide displayed encouraging neuroprotective effects in neurodegenerative disorders. This review will focus on the most promising marine drugs’ neuroprotective potential for neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. We will describe these marine compounds’ potential as adjuvant therapies for neurodegenerative diseases, based on their antioxidant, anti-inflammatory, and anti-apoptotic properties.

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Human Monocytes Plasticity in Neurodegeneration

Biomedicines ◽

10.3390/biomedicines9070717 ◽

2021 ◽

Vol 9 (7) ◽

pp. 717

Author(s):

Ilenia Savinetti ◽

Angela Papagna ◽

Maria Foti

Keyword(s):

Neurodegenerative Disorders ◽

Current Knowledge ◽

Neurological Diseases ◽

Surface Marker ◽

First Line ◽

Surface Marker Expression ◽

Physiological Properties ◽

Attractive Therapeutic Target ◽

The Brain ◽

Lateral Sclerosis

Monocytes play a crucial role in immunity and tissue homeostasis. They constitute the first line of defense during the inflammatory process, playing a role in the pathogenesis and progression of diseases, making them an attractive therapeutic target. They are heterogeneous in morphology and surface marker expression, which suggest different molecular and physiological properties. Recent evidences have demonstrated their ability to enter the brain, and, as a consequence, their hypothetical role in different neurodegenerative diseases. In this review, we will discuss the current knowledge about the correlation between monocyte dysregulation in the brain and/or in the periphery and neurological diseases in humans. Here we will focus on the most common neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis.

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Smart Design Nano-Hybrid Formulations by Machine Learning

Proceedings ◽

10.3390/iecp2020-08700 ◽

2020 ◽

Vol 78 (1) ◽

pp. 5

Author(s):

Raquel de Melo Barbosa ◽

Fabio Fonseca de Oliveira ◽

Gabriel Bezerra Motta Câmara ◽

Tulio Flavio Accioly de Lima e Moura ◽

Fernanda Nervo Raffin ◽

...

Keyword(s):

Machine Learning ◽

Experimental Data ◽

Water Solubility ◽

Inorganic Materials ◽

Fine Tuning ◽

Support Vector ◽

Drug Solubility ◽

Physical Behavior ◽

Best Fit

Nano-hybrid formulations combine organic and inorganic materials in self-assembled platforms for drug delivery. Laponite is a synthetic clay, biocompatible, and a guest of compounds. Poloxamines are amphiphilic four-armed compounds and have pH-sensitive and thermosensitive properties. The association of Laponite and Poloxamine can be used to improve attachment to drugs and to increase the solubility of β-Lapachone (β-Lap). β-Lap has antiviral, antiparasitic, antitumor, and anti-inflammatory properties. However, the low water solubility of β-Lap limits its clinical and medical applications. All samples were prepared by mixing Tetronic 1304 and LAP in a range of 1–20% (w/w) and 0–3% (w/w), respectively. The β-Lap solubility was analyzed by UV-vis spectrophotometry, and physical behavior was evaluated across a range of temperatures. The analysis of data consisted of response surface methodology (RMS), and two kinds of machine learning (ML): multilayer perceptron (MLP) and support vector machine (SVM). The ML techniques, generated from a training process based on experimental data, obtained the best correlation coefficient adjustment for drug solubility and adequate physical classifications of the systems. The SVM method presented the best fit results of β-Lap solubilization. In silico tools promoted fine-tuning, and near-experimental data show β-Lap solubility and classification of physical behavior to be an excellent strategy for use in developing new nano-hybrid platforms.

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Therapeutics potentiating microglial p21-Nrf2 axis can rescue neurodegeneration caused by neuroinflammation

Science Advances ◽

10.1126/sciadv.abc1428 ◽

2020 ◽

Vol 6 (46) ◽

pp. eabc1428

Author(s):

A. Nakano-Kobayashi ◽

A. Fukumoto ◽

A. Morizane ◽

D. T. Nguyen ◽

T. M. Le ◽

...

Keyword(s):

Neurodegenerative Disorders ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Neuronal Survival ◽

Disease Model ◽

Neuronal Loss ◽

Induced Pluripotent Stem Cell ◽

Related Factor ◽

Induced Pluripotent ◽

Novel Therapeutic

Neurodegenerative disorders are caused by progressive neuronal loss, and there is no complete treatment available yet. Neuroinflammation is a common feature across neurodegenerative disorders and implicated in the progression of neurodegeneration. Dysregulated activation of microglia causes neuroinflammation and has been highlighted as a treatment target in therapeutic strategies. Here, we identified novel therapeutic candidate ALGERNON2 (altered generation of neurons 2) and demonstrate that ALGERNON2 suppressed the production of proinflammatory cytokines and rescued neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–induced Parkinson’s disease model. ALGERNON2 stabilized cyclinD1/p21 complex, leading to up-regulation of nuclear factor erythroid 2–related factor 2 (Nrf2), which contributes to antioxidative and anti-inflammatory responses. Notably, ALGERNON2 enhanced neuronal survival in other neuroinflammatory conditions such as the transplantation of induced pluripotent stem cell–derived dopaminergic neurons into murine brains. In conclusion, we present that the microglial potentiation of the p21-Nrf2 pathway can contribute to neuronal survival and provide novel therapeutic potential for neuroinflammation-triggered neurodegeneration.

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