Synthesis of a Rivastigmine and Insulin Combinational Mucoadhesive Nanoparticle for Intranasal Delivery

Polymers, Год журнала: 2024, Номер 16(4), С. 510 - 510

Опубликована: Фев. 13, 2024

Efficient drug delivery remains a critical challenge for treating neurodegenerative diseases, such as Alzheimer’s disease (AD). Using innovative nanomaterials, delivering current medications like acetylcholinesterase inhibitors to the brain through intranasal route is promising strategy managing AD. Here, we developed unique combinational system based on N,N,N-trimethyl chitosan nanoparticles (NPs). These NPs encapsulate rivastigmine, most potent inhibitor, along with insulin, complementary therapeutic agent. The spherical exhibited zeta potential of 17.6 mV, size 187.00 nm, and polydispersity index (PDI) 0.29. Our findings demonstrate significantly improved transport efficiency sheep nasal mucosa using compared solutions. efficiencies 73.3% rivastigmine 96.9% surpassing solutions, which showed 52% 21% insulin ex vivo. results highlight new approach enhancing efficiency. mucoadhesive offer novel simultaneous cerebral could prove helpful in developing effective treatments AD other conditions.

Язык: Английский

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Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity

Frontiers in Nutrition, Год журнала: 2024, Номер 11

Опубликована: Апрель 29, 2024

Obesity, a chronic global health problem, is associated with an increase in various comorbidities, such as cardiovascular disease, type 2 diabetes mellitus, hypertension, and certain types of cancer. The increasing prevalence obesity requires research into new therapeutic strategies. Glucagon-like peptide-1 receptor agonists, specifically semaglutide liraglutide, designed for mellitus treatment, have been explored drugs the treatment obesity. This minireview describes molecular mechanisms liraglutide different metabolic pathways, its mechanism action processes appetite regulation, insulin secretion, glucose homeostasis, energy expenditure, lipid metabolism. Finally, several clinical trial outcomes are described to show safety efficacy these management.

Язык: Английский

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Sympathetic nerve-enteroendocrine L cell communication modulates GLP-1 release, brain glucose utilization, and cognitive function

Neuron, Год журнала: 2024, Номер 112(6), С. 972 - 990.e8

Опубликована: Янв. 21, 2024

Язык: Английский

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DPP-4 inhibitors sitagliptin and PF-00734,200 mitigate dopaminergic neurodegeneration, neuroinflammation and behavioral impairment in the rat 6-OHDA model of Parkinson’s disease

GeroScience, Год журнала: 2024, Номер 46(5), С. 4349 - 4371

Опубликована: Апрель 2, 2024

Epidemiological studies report an elevated risk of Parkinson's disease (PD) in patients with type 2 diabetes mellitus (T2DM) that is mitigated those prescribed dipeptidyl peptidase 4 (DPP-4) inhibitors. With objective to characterize clinically translatable doses DPP-4 inhibitors (gliptins) a well-characterized PD rodent model, sitagliptin, PF-00734,200 or vehicle were orally administered rats initiated either 7-days before after unilateral medial forebrain bundle 6-hydroxydopamine (6-OHDA) lesioning. Measures dopaminergic cell viability, dopamine content, neuroinflammation and neurogenesis evaluated thereafter ipsi- contralateral brain. Plasma brain incretin activity levels quantified. Furthermore, receptor age-dependently rodents, 6-OHDA challenged animals human subjects with/without PD. Cellular neurotrophic/neuroprotective actions combined administration. Pre-treatment oral sitagliptin reduced methamphetamine (meth)-induced rotation post-lesioning degeneration lesioned substantia nigra pars compacta (SNc) striatum. Direct intracerebroventricular gliptin administration lacked neuroprotective actions, indicating systemic incretin-mediated mechanisms underpin gliptin-induced favorable effects. Post-treatment threefold higher dose, likewise, meth-induced rotation, neurodegeneration neuroinflammation, augmented neurogenesis. These associated 70-80% plasma 20-30% inhibition, levels. Brain protein maintained preserved 6-OHDA, humans Combined GLP-1 GIP activation neuronal cultures resulted superior single agonists alone. In conclusion, these support further evaluation the repurposing approved gliptins as treatment strategy for

Язык: Английский

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Role of metabolic dysfunction and inflammation along the liver–brain axis in animal models with obesity-induced neurodegeneration

Neural Regeneration Research, Год журнала: 2024, Номер 20(4), С. 1069 - 1076

Опубликована: Май 17, 2024

The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease Parkinson’s disease. Obesity-related conditions like type 2 diabetes non-alcoholic fatty liver exacerbate this relationship. Peripheral lipid accumulation, particularly in liver, initiates a cascade inflammatory processes that extend brain, influencing critical regulatory regions. Ceramide palmitate, key components, along with transporters lipocalin-2 apolipoprotein E, contribute neuroinflammation by disrupting blood–brain barrier integrity promoting gliosis. insulin resistance further exacerbates brain neuroinflammation. Preclinical interventions targeting peripheral metabolism signaling pathways have shown promise reducing animal models. However, translating these findings clinical practice requires investigation into human subjects. In conclusion, dysfunction, inflammation, are integral neurodegeneration. Understanding complex mechanisms holds potential for identifying novel therapeutic targets improving outcomes diseases.

Язык: Английский

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An analysis on the role of glucagon-like peptide-1 receptor agonists in cognitive and mental health disorders

Nature Mental Health, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

Abstract Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are novel drugs approved for diabetes and obesity. They acknowledged as a major scientific breakthrough. In addition to their metabolic effects, these medications act on other bodily systems involved in the physiopathology of various neurological psychiatric disorders. Several stakeholders calling more research investigate repurposing potential GLP-1RAs cognitive mental disorders, while others advocate better assessment safety profile from neuropsychiatric perspective. this Analysis, we searched relevant literature effects across range illnesses, gathering describing available pre-clinical mechanistic (278 studies) clinical (96 evidence substance-use psychotic mood anxiety eating others. By leveraging translational insights data, consider implications practice propose avenues further research.

Язык: Английский

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GLP-1RA and SGLT2i Medications for Type 2 Diabetes and Alzheimer Disease and Related Dementias

JAMA Neurology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Importance The association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) risk of Alzheimer disease related dementias (ADRD) remains to be confirmed. Objective To assess the ADRD associated with GLP-1RAs SGLT2is in people type 2 diabetes (T2D). Design, Setting, Participants This target trial emulation study used electronic health record data from OneFlorida+ Clinical Research Consortium January 2014 June 2023. Patients were 50 years or older T2D no prior diagnosis antidementia treatment. Among 396 963 eligible patients T2D, 33 858 included GLP-1RA vs other glucose-lowering drug (GLD) cohort, 34 185 SGLT2i GLD 24 117 cohort. Exposures Initiation treatment a GLP-1RA, SGLT2i, second-line GLD. Main Outcomes Measures was identified using clinical codes. Hazard ratios (HRs) 95% CIs estimated Cox proportional hazard regression models inverse probability weighting (IPTW) adjust for potential confounders. Results cohort (mean age, 65 years; 53.1% female), 65.8 49.3% 63.8 51.7% female). In IPTW-weighted cohorts, incidence rate lower initiators compared (rate difference [RD], −2.26 per 1000 person-years [95% CI, −2.88 −1.64]), yielding an HR 0.67 (95% 0.47-0.96). had than (RD, −3.05 −3.68 −2.42]), 0.57 0.43-0.75). There SGLT2is, RD −0.09 −0.80 0.63) 0.97 0.72-1.32). Conclusion Relevance both statistically significantly decreased GLDs, observed drugs.

Язык: Английский

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Diabetes-Alzheimer's connection in older age: SGLT2 inhibitors as promising modulators of disease pathways

Ageing Research Reviews, Год журнала: 2023, Номер 90, С. 102018 - 102018

Опубликована: Июль 20, 2023

Язык: Английский

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Mitochondria and Oxidative Stress as a Link between Alzheimer’s Disease and Diabetes Mellitus

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14450 - 14450

Опубликована: Сен. 22, 2023

This review is devoted to the problems of common features linking metabolic disorders and type 2 diabetes with development Alzheimer’s disease. The pathogenesis disease closely intersects mechanisms development, an important risk factor for both pathologies aging. Common pathological include factors in oxidative stress, neuroinflammation, insulin resistance, amyloidosis, as well impaired mitochondrial dysfunctions increasing cell death. currently available drugs treatment have limited therapeutic efficacy. It note that used treat disease, particular acetylcholinesterase inhibitors, show a positive potential diabetes, while can also prevent number characteristic A promising direction search strategy may be creation complex multi-target neuroprotective affect specific targets

Язык: Английский

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Metabolic hormones are integral regulators of female reproductive health and function

Bioscience Reports, Год журнала: 2023, Номер 44(1)

Опубликована: Дек. 22, 2023

The female reproductive system is strongly influenced by nutrition and energy balance. It well known that food restriction or depletion can induce suppression of processes, while overnutrition associated with dysfunction. However, the intricate mechanisms through which nutritional inputs metabolic health are integrated into coordination reproduction still being defined. In this review, we describe evidence for essential contributions hormones responsive to intake fuel stores. Key hormones-including insulin, incretins (glucose-dependent insulinotropic polypeptide glucagon-like peptide-1), growth hormone, ghrelin, leptin, adiponectin-signal throughout hypothalamic-pituitary-gonadal axis support suppress reproduction. We synthesize current knowledge on how these multifaceted interact brain, pituitary, ovaries regulate functioning system, incorporating in vitro vivo data from animal models humans. Metabolic involved orchestrating processes healthy states, but some also play a significant role pathophysiology treatment strategies disorders. Further understanding complex interrelationships between function has important implications improving women's overall.

Язык: Английский

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