Oxcarbazepine free or loaded PLGA nanoparticles as effective intranasal approach to control epileptic seizures in rodents

Musumeci, Teresa; Serapide, Maria Francesca; Pellitteri, Rosalia; Dalpiaz, Alessandro; Ferraro, Luca; Magro, Roberta Dal; Bonaccorso, Angela; Carbone, Claudia; Veiga, Francisco; Sancini, Giulio; Puglisi, Giovanni

doi:10.1016/j.ejpb.2018.11.002

Cited by 83 publications

(50 citation statements)

References 40 publications

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“…Moreover, PLGA nanoparticles were shown to display an increased uptake by the olfactory unsheathing cells when compared to PLA nanoparticles [32]. PLGA 65/35-HPC-GAL nanoparticles showed an average size of 240 nm (Table 2), and existing literature suggests that PLGA nanoparticles of an average size of <300 nm are capable of entering the brain just a few hours after their IN administration in adult Wistar rats [33]. Taking into account all the above, the PLGA 65/35-HPC-GAL nanoparticles were expected to be more effectively delivered to the brain by comparison to the significantly larger PLGA 75/25-HPC-GAL (393.959 ± 0.39 nm) and PLLA-HPC-GAL nanoparticles (1302.06 ± 0.49 nm).…”

Section: Selection and Fluorescence Evaluation Of Rhodamine-treated Pmentioning

confidence: 94%

“…Pharmaceutics 2020, 12, 227 18 of 22 their IN administration in adult Wistar rats [33]. Taking into account all the above, the PLGA 65/35-HPC-GAL nanoparticles were expected to be more effectively delivered to the brain by comparison to the significantly larger PLGA 75/25-HPC-GAL (393.959 ± 0.39 nm) and PLLA-HPC-GAL nanoparticles (1302.06 ± 0.49 nm).…”

Section: Selection and Fluorescence Evaluation Of Rhodamine-treated Pmentioning

confidence: 99%

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Hierarchical Porous Carbon—PLLA and PLGA Hybrid Nanoparticles for Intranasal Delivery of Galantamine for Alzheimer’s Disease Therapy

et al. 2020

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In the present study, poly(l-lactic acid) (PLLA) and poly(lactide-co-glycolide) (PLGA) hybrid nanoparticles were developed for intranasal delivery of galantamine, a drug used in severe to moderate cases of Alzheimer's disease. Galantamine (GAL) was adsorbed first in hierarchical porous carbon (HPC). Formulations were characterized by FT-IR, which showed hydrogen bond formation between GAL and HPC. Furthermore, GAL became amorphous after adsorption, as confirmed by XRD and differential scanning calorimetry (DSC) studies. GAL was quantified to be 21.5% w/w by TGA study. Adsorbed GAL was nanoencapsulated in PLLA and PLGA, and prepared nanoparticles were characterized by several techniques. Their sizes varied between 182 and 394 nm, with an exception that was observed in nanoparticles that were prepared by PLLA and adsorbed GAL that was found to be 1302 nm in size. DSC thermographs showed that GAL was present in its crystalline state in nanoparticles before its adsorption to HPC, while it remained in its amorphous phase after its adsorption in the prepared nanoparticles. It was found that the polymers controlled the release of GAL both when it was encapsulated alone and when it was adsorbed on HPC. Lastly, PLGA hybrid nanoparticles were intranasally-administered in healthy, adult, male Wistar rats. Administration led to successful delivery to the hippocampus, the brain area that is primarily and severely harmed in Alzheimer's disease, just a few hours after a single dose.

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Section: Selection and Fluorescence Evaluation Of Rhodamine-treated Pmentioning

confidence: 94%

Section: Selection and Fluorescence Evaluation Of Rhodamine-treated Pmentioning

confidence: 99%

Hierarchical Porous Carbon—PLLA and PLGA Hybrid Nanoparticles for Intranasal Delivery of Galantamine for Alzheimer’s Disease Therapy

et al. 2020

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“…It has been shown that olanzapine PLGA nanoparticles resulted in 10-times more Cmax and drug delivery to the brain than olanzapine solution [182]. A study reported that oxcarbazepine PLGA nanoparticles showed better pharmacokinetic behavior and superiorly reduced intraperitoneal pentylene tetrazole-induced seizures in a rat model than the drug in solution form [204]. It was shown that upon intranasal administration, a PLGA-poly(ethylene glycol) (PLGA-PEG) copolymer nanoparticle, conjugated with Solanum tuberosum lectin and loaded with basic fibroblast growth factor, improved cognition in a mouse AD model [205].…”

Section: Nanoparticles Composed Of Chitosan and Chitosan Derivativesmentioning

confidence: 99%

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

et al. 2020

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Although the global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs' entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices. Figure 1. Schematic demonstrating various transport systems that shuttle molecules across the BBB. Very small amount of water-soluble compounds cross through the tight junctions (paracellular), whereas lipid-soluble agents traverse via the transcellular lipophilic pathway. Selective transport systems exist for glucose, amino acids, nucleosides, and other substances, in addition to specific receptor-mediated endocytosis for certain proteins such as insulin and transferrin. (AZT = azathioprine). List of CNS Diseases Parkinson's Disease (PD)PD, occurring primarily in the substantia nigra, is the second-most common neurodegenerative disease, leading to the development of bradykinesia and tremors of cardinal motor functions ( Figure 2) [3]. PD models specifically show a decrease in dopamine transporters, which are responsible for dopamine uptake by dopaminergic neurons and progression of neuronal communications. Reduced Figure 1. Schematic demonstrating various transport systems that shuttle molecules across the BBB. Very small amount of water-soluble compounds cross through the tight junctions (paracellular), whereas lipid-soluble agents traverse via the transcellular lipophilic pathway. Selective transport systems exist for glucose, amino acids, nucleosides, and other substances, in addition to specific receptor-mediated endocytosis for certain proteins such as insulin and transferrin. (AZT = azathioprine). List of CNS Diseases Parkinson's Disease (PD)PD, occurring primarily in the substantia nigra, is the second-most common neuro...

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“…Olanzapine, when loaded onto PLGA nanoparticles, resulted in delivery to the brain that was 10 times more efficient than Nose-to-Brain Delivery nose-to-brain delivery with olanzapine solution, resulting in a C max of 0.049% of the dose and a C max of 0.0045% of the dose with the nanoparticle and solution formulations, respectively (Seju et al, 2011). As well as pharmacokinetics evidence of nose-to-brain transport, pharmacodynamics evidence of nose-to-brain transport has been recorded in the form of a reduction in seizures in a rat seizure model, using PLGA nanoparticles (Musumeci et al, 2018). PLGA nanoparticulate oxcarbazepine reduced seizures in a rat seizure model (seizures induced by intraperitoneal pentylene tetrazole) on intranasal administration, and the nanoparticles were superior to the drug in solution in protecting against seizures (Musumeci et al, 2018).…”

Section: Nanoparticlesmentioning

confidence: 99%

Nose-to-Brain Delivery

Wang¹,

Xiong²,

Tsang³

et al. 2019

J Pharmacol Exp Ther

168

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The global prevalence of neurologic disorders is rising, and yet we are still unable to deliver most drug molecules, in therapeutic quantities, to the brain. The blood brain barrier consists of a tight layer of endothelial cells surrounded by astrocyte foot processes, and these anatomic features constitute a significant barrier to drug transport from the blood to the brain. One way to bypass the blood brain barrier and thus treat diseases of the brain is to use the nasal route of administration and deposit drugs at the olfactory region of the nares, from where they travel to the brain via mechanisms that are still not clearly understood, with travel across nerve fibers and travel via a perivascular pathway both being hypothesized. The nose-to-brain route has been demonstrated repeatedly in preclinical models, with both solution and particulate formulations. The nose-to-brain route has also been demonstrated in human studies with solution and particle formulations. The entry of device manufacturers into the arena will enable the benefits of this delivery route to become translated into approved products. The key factors that determine the efficacy of delivery via this route include the following: delivery to the olfactory area of the nares as opposed to the respiratory region, a longer retention time at the nasal mucosal surface, penetration enhancement of the active through the nasal epithelia, and a reduction in drug metabolism in the nasal cavity. Indications where nose-to-brain products are likely to emerge first include the following: neurodegeneration, posttraumatic stress disorder, pain, and glioblastoma.

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Oxcarbazepine free or loaded PLGA nanoparticles as effective intranasal approach to control epileptic seizures in rodents

Cited by 83 publications

References 40 publications

Hierarchical Porous Carbon—PLLA and PLGA Hybrid Nanoparticles for Intranasal Delivery of Galantamine for Alzheimer’s Disease Therapy

Hierarchical Porous Carbon—PLLA and PLGA Hybrid Nanoparticles for Intranasal Delivery of Galantamine for Alzheimer’s Disease Therapy

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Nose-to-Brain Delivery

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