Simvastatin is delivered to the brain by high-strength intranasal cationic SMEDDS and nanoemulsions.

The repurposing of statins as neuroprotective agents and/or anti-brain tumor drugs is limited by challenges in brain bioavailability and systemic off-target effects. Therefore, improved and targeted delivery of statins to the brain is necessary. This study aimed to develop a high-strength liquid formulation of the poorly soluble prodrug simvastatin for intranasal administration, as a strategy to achieve high brain concentrations of the prodrug and/or its active form, tenivastatin.

The impact of extract on pharmacokinetics of phenytoin in rats.

Epilepsy patients are at a higher risk of developing overweight and obesity. Given the thermogenic properties of (Guarana), this study aimed to evaluate a potential pharmacokinetic interaction between extract and phenytoin in rats. Two pharmacokinetic studies were developed with and phenytoin: a coadministration and a pre-treatment study.

Differential response of blueberry to the application of bacterial inoculants to improve yield, organoleptic qualities and concentration of bioactive compounds.

The application of bacterial biofortifiers is an increasingly common technique. In recent years, some strains have been shown to improve the nutraceutical qualities of crops. This work analyses the impact of biofortification with 3 bacterial strains of the genera Rhizobium, Paenibacillus and Lactiplantibacillus on the nutritional characteristics and organic composition of blueberry in Portugal.

Innovative Aqueous Nanoemulsion Prepared by Phase Inversion Emulsification with Exceptional Homogeneity.

Formulating low-solubility or low-permeability drugs is a challenge, particularly with the low administration volumes required in intranasal drug delivery. Nanoemulsions (NE) can solve both issues, but their production and physical stability can be challenging, particularly when a high proportion of lipids is necessary. Hence, the aim of the present work was to develop a NE with good solubilization capacity for lipophilic drugs like simvastatin and able to promote the absorption of drugs with low permeability like fosphenytoin.

Intranasal Microemulsion as an Innovative and Promising Alternative to the Oral Route in Improving Stiripentol Brain Targeting.

Stiripentol (STP) is a new-generation antiepileptic only available for oral administration. However, it is extremely unstable in acidic environments and undergoes gastrointestinal slow and incomplete dissolution. Thus, STP intranasal (IN) administration might overcome the high oral doses required to achieve therapeutic concentrations.

Nose-to-brain delivery of perampanel formulated in a self-microemulsifying drug delivery system improves anticonvulsant and anxiolytic activity in mice.

Perampanel (PER) is a potent third-generation antiepileptic drug only available for oral administration. Additionally, PER has shown potential in managing epilepsy comorbidities such as anxiety. Previously, we demonstrated that the intranasal (IN) administration of PER, loaded in a self-microemulsifying drug delivery system (SMEDDS), improved brain-targeting and exposure in mice.

Insight into the Taxonomic and Functional Diversity of Bacterial Communities Inhabiting Blueberries in Portugal.

is a dwarf shrub of the family with a Palearctic distribution, associated with temperate and cold humid climates. It is widespread on the European continent; on the Iberian Peninsula it is located on Atlantic climate mountains and glacial relicts. In Portugal, we find scattered and interesting populations; however, the majority of them are threatened by climate change and wildfires.

Self-Emulsifying Drug Delivery Systems: An Alternative Approach to Improve Brain Bioavailability of Poorly Water-Soluble Drugs through Intranasal Administration.

Efforts in discovering new and effective neurotherapeutics are made daily, although most fail to reach clinical trials. The main reason is their poor bioavailability, related to poor aqueous solubility, limited permeability through biological membranes, and the hepatic first-pass metabolism. Nevertheless, crossing the blood-brain barrier is the major drawback associated with brain drug delivery.

Intranasal delivery of lipid-based nanosystems as a promising approach for brain targeting of the new-generation antiepileptic drug perampanel.

Perampanel (PER), a new-generation antiepileptic drug effective against different types of seizures, has already demonstrated a potential in status epilepticus therapy. Considering the growing interest of intranasal (IN) administration for nose-to-brain delivery, PER could be envisioned as a good candidate for this route, especially if formulated in a lipid-based nanosystem. With that purpose, a hydrophobic formulation (FO1.

Study of the metabolic stability profiles of perampanel, rufinamide and stiripentol and prediction of drug interactions using HepaRG cells as an in vitro human model.

New-generation antiepileptic drugs as perampanel, rufinamide and stiripentol emerged as alternatives in chronic epilepsy polytherapy. Hence, their metabolic stability and potential involvement in relevant drug-drug interactions (DDI) are of great clinical interest, being HepaRG cells herein used as an in vitro human model. To characterize their metabolic stability profiles, HepaRG cells were incubated with perampanel (1 μM), rufinamide (100 μM) or stiripentol (5 μM) for 12-h.

Liquid chromatographic methods for determination of the new antiepileptic drugs stiripentol, retigabine, rufinamide and perampanel: A comprehensive and critical review.

The new antiepileptic drugs perampanel, retigabine, rufinamide and stiripentol have been recently approved for different epilepsy types. Being them an innovation in the antiepileptics armamentarium, a lot of investigations regarding their pharmacological properties are yet to be performed. Besides, considering their broad anticonvulsant activities, an extension of their therapeutic indications may be worthy of investigation, especially regarding other seizure types as well as other central nervous system disorders.

Salting-out assisted liquid-liquid extraction method optimized by design of experiments for the simultaneous high-performance liquid chromatography analysis of perampanel and stiripentol in mouse matrices.

We report a high-performance liquid chromatography method development able to simultaneously determine perampanel and stiripentol, two third-generation antiepileptics whose therapeutic spectrum can potentially be extended, in several mouse matrices. A salting-out assisted liquid-liquid extraction optimized by a design of experiments approach was adopted for sample preparations. Isopropanol and magnesium sulfate were the extraction solvent and salting-out agent, respectively.

Novel bioanalytical method for the quantification of rufinamide in mouse plasma and tissues using HPLC-UV: A tool to support pharmacokinetic studies.

Rufinamide is an antiepileptic drug approved for seizures treatment associated with Lennox-Gastaut syndrome. To support future pharmacokinetic studies in rodents, this work aimed to validate for the first time a fast and simple high-performance liquid chromatographic (HPLC) method for rufinamide quantification in mouse plasma and brain, liver and kidney tissues. For that, aliquots (100 μL) of plasma or tissues homogenates were spiked with known amounts of rufinamide and chloramphenicol (internal standard).

Silymarin as a flavonoid-type P-glycoprotein inhibitor with impact on the pharmacokinetics of carbamazepine, oxcarbazepine and phenytoin in rats.

P-glycoprotein (P-gp) is an efflux transporter involved in drug-resistant epilepsy and some flavonoids have been targeted as effective P-gp inhibitors. Herein, we assessed the impact of silymarin on the pharmacokinetics of three antiepileptic drugs (AEDs) in rats. Animals were pretreated with silymarin, verapamil (positive control) or vehicle (negative control) 1 h before AEDs administration (carbamazepine (25 mg/kg), oxcarbazepine (OXC) (50 mg/kg), or phenytoin (100 mg/kg)).

Drug-Induced Epistaxis: An Often-Neglected Adverse Effect.

Background: Epistaxis is an active nose bleeding with a population occurrence of approximately 60%. Although epistaxis is a common clinical complaint, the majority of the cases are benign and caused by local induced factors (e.g.