Amelioration of oxidative stress utilizing nanoemulsion loaded with bromocriptine and glutathione for the management of Parkinson's disease

Ashhar, Muhammad Usama; Vyas, Preeti; Vohora, Divya; Sahoo, PK; Nigam, Kuldeep; Dang, Shweta; Ali, Javed; Baboota, Sanjula

doi:10.1016/j.ijpharm.2022.121683

Cited by 11 publications

(5 citation statements)

References 49 publications

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“…Absence of pathological change and irritation during nasal cilio toxicity study demonstrated preliminary safety and biocompatibility of CONPs. Similar to our results, nasal safety of CONPs was also reported previously (Usama Ashhar et al, 2022).…”

Section: Discussionsupporting

confidence: 93%

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Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats

Mohammad,

Khan,

Warsi

et al. 2023

Front. Pharmacol.

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Introduction: Cerium oxide nanoparticles (CONPs) have been investigated for their therapeutic potential in Parkinson’s disease (PD) due to their potent and regenerative antioxidant activity. In the present study, CONPs were used to ameliorate the oxidative stress caused by free radicals in haloperidol-induced PD in rats following intranasal administration.Method: The antioxidant potential of the CONPs was evaluated in vitro using ferric reducing antioxidant power (FRAP) assay. The penetration and local toxicity of the CONPs was evaluated ex-vivo using goat nasal mucosa. The acute local toxicity of intranasal CONPs was also studied in rat. Gamma scintigraphy was used to assess the targeted brain delivery of CONPs. Acute toxicity studies were performed in rats to demonstrate safety of intranasal CONPs. Further, open field test, pole test, biochemical estimations and brain histopathology was performed to evaluate efficacy of intranasal CONPs in haloperidol-induced PD rat model.Results: The FRAP assay revealed highest antioxidant activity of prepared CONPs at a concentration of 25 μg/mL. Confocal microscopy showed deep and homogenous distribution of CONPs in the goat nasal mucus layers. No signs of irritation or injury were seen in goat nasal membrane when treated with optimized CONPs. Scintigraphy studies in rats showed targeted brain delivery of intranasal CONPs and acute toxicity study demonstrated safety. The results of open field and pole test showed highly significant (p < 0.001) improvement in locomotor activity of rats treated with intranasal CONPs compared to untreated rats. Further, brain histopathology of treatment group rats showed reduced neurodegeneration with presence of more live cells. The amount of thiobarbituric acid reactive substances (TBARS) was reduced significantly, whereas the levels of catalase (CAT), superoxide dismutase (SOD), and GSH were increased significantly, while amounts of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) showed significant reduction after intranasal administration of CONPs. Also, the intranasal CONPs, significantly high (p < 0.001) dopamine concentration (13.93 ± 0.85 ng/mg protein) as compared to haloperidol-induced control rats (5.76 ± 0.70 ng/mg protein).Conclusion: The overall results concluded that the intranasal CONPs could be safe and effective therapeutics for the management of PD.

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Section: Discussionsupporting

confidence: 93%

“…Following this, sections were collected, stained with haematoxylin and eosin and analysed for histopathological changes using microscope at 100× magnification. ( Usama Ashhar et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats

Mohammad,

Khan,

Warsi

et al. 2023

Front. Pharmacol.

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“…Increased oxidative stress and mitochondrial reactive oxygen species production have been demonstrated in the diabetic retina [52,53]. By reducing oxidative damage and enhancing the quality control machinery of mitochondria, therapeutic approaches, such as using resveratrol and bromocriptine (a dopamine receptor D2 agonist), appear to be promising interventions to halt the development and progression of DR [54][55][56][57].…”

Section: Discussionmentioning

confidence: 99%

Functional and structural changes in the neuroretina are accompanied by mitochondrial dysfunction in a type 2 diabetic mouse model

Lam,

Zou,

Chan

et al. 2023

Eye and Vis

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Background Diabetic retinopathy (DR), one of the leading causes of blindness and vision impairment, is suggested to exhibit functional and structural changes in retinal neurons as the earliest manifestation, which could be used to predict the progression of related angiopathy. While neural function and survival rely on proper mitochondrial function, and a growing body of literature has supported the role of mitochondrial dysfunction in the development of DR, how diabetes affects mitochondrial function in retinal tissue remains elusive. This study primarily aimed to investigate mitochondrial functional changes in a diabetic rodent model. We also characterized the early DR phenotype, in particular, neurodegeneration. Methods C57BLKsJ-db/db (db/db) mice (a type 2 diabetic mouse model) were used with their normoglycemic heterozygous littermates (db/+) serving as controls. Longitudinal changes in retinal function and morphology were assessed with electroretinography (ERG) and optical coherence tomography (OCT), respectively, at 9, 13, 17, and 25 weeks of age. At 25 weeks, the retinas were harvested for immunohistochemistry and ex vivo mitochondrial bioenergetics. Results Decreased ERG responses were observed in db/db mice as early as 13 weeks of age. OCT revealed that db/db mice had significantly thinner retinas than the controls. Immunohistochemistry showed that the retinas of the db/db mice at 25 weeks were thinner at the outer and inner nuclear layers, with lower photoreceptor and cone cell densities compared with the db/+ mice. The number of rod-bipolar cell dendritic boutons and axon terminals was significantly reduced in db/db mice relative to the db/+ mice, suggesting that diabetes may lead to compromised synaptic connectivity. More importantly, the retinas of db/db mice had weaker mitochondrial functions than the controls. Conclusions Our longitudinal data suggest that diabetes-induced functional deterioration and morphological changes were accompanied by reduced mitochondrial function in the retina of db/db mice. These findings suggest that mitochondrial dysfunction may be a contributing factor triggering the development of DR. While the underlying mechanistic cause remains elusive, the db/db mice could be a useful animal model for testing potential treatment regimens targeting neurodegeneration in DR.

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“…The ability of NEs to transport lurasidone for the prospective therapy of schizophrenia was also revealed [ 164 ]. Other examples of NEs used for delivering drugs from the nose to the brain include curcumin NE, which has anti-inflammatory characteristics [ 165 , 166 ], tacrine NE, used for treating Alzheimer’s disease [ 167 ], risperidone NEs, which serves as a delivery mechanism for antipsychotic drugs [ 168 ], resveratrol NEs used for neurodegenerative disorders [ 169 ], and bromocriptine NE, which enhances brain targeting [ 170 ]. These formulations are designed to address the difficulties related to the limited capacity of medications to dissolve and be absorbed by the body, providing a promising approach for the effective transport of pharmaceuticals from the nose-to-brain route.…”

Section: Nanoparticles For Nose-to-brain Drug Deliverymentioning

confidence: 99%

Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport

Gandhi,

Shastri,

Shah

et al. 2024

Pharmaceutics

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The nose-to-brain drug-delivery system has emerged as a promising strategy to overcome the challenges associated with conventional drug administration for central nervous system disorders. This emerging field is driven by the anatomical advantages of the nasal route, enabling the direct transport of drugs from the nasal cavity to the brain, thereby circumventing the blood–brain barrier. This review highlights the significance of the anatomical features of the nasal cavity, emphasizing its high permeability and rich blood supply that facilitate rapid drug absorption and onset of action, rendering it a promising domain for neurological therapeutics. Exploring recent developments and innovations in different nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, micelles, nanoemulsions, nanosuspensions, carbon nanotubes, mesoporous silica nanoparticles, and nanogels unveils their diverse functions in improving drug-delivery efficiency and targeting specificity within this system. To minimize the potential risk of nanoparticle-induced toxicity in the nasal mucosa, this article also delves into the latest advancements in the formulation strategies commonly involving surface modifications, incorporating cutting-edge materials, the adjustment of particle properties, and the development of novel formulations to improve drug stability, release kinetics, and targeting specificity. These approaches aim to enhance drug absorption while minimizing adverse effects. These strategies hold the potential to catalyze the advancement of safer and more efficient nose-to-brain drug-delivery systems, consequently revolutionizing treatments for neurological disorders. This review provides a valuable resource for researchers, clinicians, and pharmaceutical-industry professionals seeking to advance the development of effective and safe therapies for central nervous system disorders.

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Amelioration of oxidative stress utilizing nanoemulsion loaded with bromocriptine and glutathione for the management of Parkinson's disease

Cited by 11 publications

References 49 publications

Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats

Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats

Functional and structural changes in the neuroretina are accompanied by mitochondrial dysfunction in a type 2 diabetic mouse model

Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport

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