Design and optimization of metformin-loaded solid lipid nanoparticles for neuroprotective effects in a rat model of diffuse traumatic brain injury: A biochemical, behavioral, and histological study

Ebrahimi, Hossein Ali; Nezhad, Sajjad Kazem; Farmoudeh, Ali; Babaei, Amirhossein; Ebrahimnezhad, Pedram; Akbari, Esmaeil; Siahposht-Khachaki, Ali

doi:10.1016/j.ejpb.2022.10.018

Cited by 13 publications

(6 citation statements)

References 57 publications

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“…Thermogram of GMS showed an endothermic peak with the midpoint of around 65°C corresponding to melting point of GMS 39 . In brief, the characteristic peaks of pure LCZ and pure GMS disappeared, which showed an effective incorporation of LCZ in the lipid that led to NLC preparation and drug encapsulation.…”

Section: Dsc Thermogram Investigationmentioning

confidence: 99%

Formulation, characterization, and in vitro antifungal efficacy of luliconazole-loaded nanostructured lipid carriers (LCZ-NLCs) against a panel of resistant fungal strains

Nosratabadi,

Barogh,

Rahimnia

et al. 2024

Preprint

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Luliconazole (LCZ) is a topical imidazole antifungal agent with broad-spectrum activity. However, LCZ faces challenges like low aqueous solubility, skin retention, and penetration, limiting its dermal bioavailability and effectiveness in drug delivery. This study aims to formulate, characterize, and assess the in vitro antifungal efficacy of luliconazole-loaded nanostructured lipid carriers (LCZ-NLCs) against resistant fungal strains. The LCZ-NLCs were synthesized using a modified emulsification-solvent evaporation method. Characterization included poly-dispersity index (PDI), zeta potential, entrapment efficiency (EE %), Field Emission Scanning Electron Microscopy (FESEM), Differential Scanning Calorimetry (DSC) analysis, and Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) study. Additionally, in vitro drug release experiments, kinetic analysis of release data, cytotoxicity assays, and in vitro antifungal susceptibility tests were conducted. The results revealed that LCZ-NLCs exhibited nanoscale dimensions, uniform dispersion, and a favorable zeta potential. The encapsulation efficiency of LCZ in NLCs was around 90%. FESEM analysis showed spherical nanoparticles with consistent shape. ATR-FTIR analysis indicated no chemical interaction between LCZ and excipients. In vitro drug release experiments suggested that LCZ-NLCs significantly improved the drug's dissolution rate. Stability testing also showed consistent colloidal nanometer ranges in LCZ-NLCs samples. Also, cytotoxicity tests showed no toxicity within the tested concentration. Furthermore, in vitro antifungal susceptibility tests demonstrated potent antifungal activity of both LCZ and LCZ-NLCs against resistant fungal isolates. The study findings suggest that the LCZ-NLCs formulation developed in this research could be a promising topical treatment for superficial fungal infections, especially in cases of resistant infections.

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Section: Dsc Thermogram Investigationmentioning

confidence: 99%

Formulation, characterization, and in vitro antifungal efficacy of luliconazole-loaded nanostructured lipid carriers (LCZ-NLCs) against a panel of resistant fungal strains

Nosratabadi,

Barogh,

Rahimnia

et al. 2024

Preprint

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“…Marmarou WD mainly replicates diffuse axonal injury caused by external violence injury such as high altitude fall injury and traffic accident, and Marmarou WD causes extensive and bilateral damage to neurons, axons, dendrites and microvessels, especially in the corpus callosum, internal capsule, optic nerve bundle and other parts. It may also lead to motor and cognitive deficits, such as difficulty walking and memory, which are related to the severity of the injury ( 10 , 14 , 15 , 21 , 24 ).…”

Section: Mechanical Force Injury Modelsmentioning

confidence: 99%

“…Different animal models have been established to replicate different types of TBI. Although larger animals are more similar to humans in size and physiology, rodents have been widely used in TBI models because of their small size, low cost and easy quantification ( 10 , 11 ). Early TBI models mainly simulated the biomechanical changes of brain injury, while the models created in recent years have been used to study molecular mechanisms and molecular cascades triggered by head trauma ( 11–13 ).…”

Section: Introductionmentioning

confidence: 99%

Models of traumatic brain injury-highlights and drawbacks

Zhao

Zhang

et al. 2023

Front. Neurol.

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Traumatic brain injury (TBI) is the leading cause for high morbidity and mortality rates in young adults, survivors may suffer from long-term physical, cognitive, and/or psychological disorders. Establishing better models of TBI would further our understanding of the pathophysiology of TBI and develop new potential treatments. A multitude of animal TBI models have been used to replicate the various aspects of human TBI. Although numerous experimental neuroprotective strategies were identified to be effective in animal models, a majority of strategies have failed in phase II or phase III clinical trials. This failure in clinical translation highlights the necessity of revisiting the current status of animal models of TBI and therapeutic strategies. In this review, we elucidate approaches for the generation of animal models and cell models of TBI and summarize their strengths and limitations with the aim of exploring clinically meaningful neuroprotective strategies.

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“…Similar advancements showed promising results when targeting the brain specifically, which is vital in potential glioblastoma treatments. Lipid nanoparticles, borneol W/O/W composite submicron emulsions, and exosomes have shown increased metformin delivery to brain tissue compared to typical free metformin drug administration [ 78 , 79 , 80 ]. The exosome technology involved removing naturally created exosomes from the blood, loading them with metformin or the desired drug, and injecting the loaded exosomes as a therapeutic: not only did the exosomes cross the BBB, but they seemed to specifically accumulate in glioblastoma cells [ 80 , 81 ].…”

Section: Clinical Considerations and Relevancementioning

confidence: 99%

Could Metformin and Resveratrol Support Glioblastoma Treatment? A Mechanistic View at the Cellular Level

Ibrahim

El-Naas

et al. 2023

Cancers

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Glioblastoma, a malignant brain tumor, is a common primary brain tumor in adults, with diabetes mellitus being a crucial risk factor. This review examines how the antidiabetic drug metformin and dietary supplement resveratrol can benefit the treatment of glioblastoma. Metformin and resveratrol have demonstrated action against relevant pathways in cancer cells. Metformin and resveratrol inhibit cell proliferation by downregulating the PI3K/Akt pathway, activating mTOR, and increasing AMPK phosphorylation, resulting in lower proliferation and higher apoptosis levels. Metformin and resveratrol both upregulate and inhibit different cascades in the MAPK pathway. In vivo, the drugs reduced tumor growth and volume. These actions show how metformin and resveratrol can combat cancer with both glucose-dependent and glucose-independent effects. The pre-clinical results, alongside the lack of clinical studies and the rise in novel delivery mechanisms, warrant further clinical investigations into the applications of metformin and resveratrol as both separate and as a combination complement to current glioblastoma therapies.

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Design and optimization of metformin-loaded solid lipid nanoparticles for neuroprotective effects in a rat model of diffuse traumatic brain injury: A biochemical, behavioral, and histological study

Cited by 13 publications

References 57 publications

Formulation, characterization, and in vitro antifungal efficacy of luliconazole-loaded nanostructured lipid carriers (LCZ-NLCs) against a panel of resistant fungal strains

Formulation, characterization, and in vitro antifungal efficacy of luliconazole-loaded nanostructured lipid carriers (LCZ-NLCs) against a panel of resistant fungal strains

Models of traumatic brain injury-highlights and drawbacks

Could Metformin and Resveratrol Support Glioblastoma Treatment? A Mechanistic View at the Cellular Level

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