Assessment of Nasal-Brain-Targeting Efficiency of New Developed Mucoadhesive Emulsomes Encapsulating an Anti-Migraine Drug for Effective Treatment of One of the Major Psychiatric Disorders Symptoms

Abstract

Migraine is one of the major symptoms of many psychiatric and mental disorders like depression and anxiety. Eletriptan Hydrobromide (EH) is a well-tolerated drug in migraine treatment, but suffers from low oral bioavailability and low brain targeting after oral delivery. New nasal mucoadhesive EH-emulsomes development could be a new means to direct the drug from the nose-to-brain to achieve rapid onset of action and high drug concentration in the brain for acute migraine treatment. Eletriptan mucoadhesive emulsomes formulations were prepared using thin-film hydration method and 23 full factorial design was adopted to study different formulation factors’ effect on the emulsomes characters. The emulsomes were characterized for entrapment efficiency (EE%), zeta potential (ZP), particle size (PS), morphology, and ex-vivo permeation through the nasal mucosa. The selected formula was evaluated in mice for its in-vivo bio-distribution in comparison with EH intranasal and intravenous solutions. Drug targeting efficacy (DTE%) and nose-to-brain direct transport percentage (DTP%) were calculated. The optimization formulation showed a nanoparticle size of 177.01 nm, EE 79.44%, and ZP = 32.12 ± 3.28 mV. In addition, in-vitro permeability studies revealed enhanced drug permeability with suitable mean residence time up to 120 ± 13 min. EH-emulsomes were stable under different storage conditions for three months. In vivo examination and pharmacokinetic drug targeting parameters revealed EH transport to the CNS after EH nanoparticle nasal administration. Histopathology study showed no ciliotoxic effect on the nasal mucosa. From the results, it can be confirmed that the emulsomes formulation of EH proved safe direct nose-to-brain transport of EH after nasal administration of EH emulsomes.

Repurposing of atorvastatin emulsomes as a topical antifungal agent

“…As mentioned in the study by Abo El-Enin et al. upon studying an emulsome system loaded with eletriptan hydrobromide using PC in different molar ratios with compritol, a reduction in PS was reported with a higher PC amount as more emulsome vesicles may be formed (Abo El-Enin et al., 2022 ). These findings agreed with reported results of E12.…”

Formulation and Characterization of Intranasal Drug Delivery of Frovatriptan-Loaded Binary Ethosomes Gel for Brain Targeting

“…Where “Bx” represents the brain “AUC” fraction contributed by systemic circulation through the blood-brain barrier following (IN) administration, B IV is the AUC 0–360 (brain) following IV administration, P IV is the AUC 0–360 (blood) following IV administration, B IN is the AUC 0–360 (brain) following IN administration, P IN is the AUC 0–360 (blood) following IN administration. 45 , 62 …”

“…Following intravenous injection, the absolute (F a ) and relative (F r ) bioavailabilities of FVT were estimated using the following equations: 61 To evaluate brain targeting efficiency, two indices, namely drug targeting efficiency (DTE%) and brain drug direct transport percentage (DTP%), were calculated using the following equations: 61 Where "Bx" represents the brain "AUC" fraction contributed by systemic circulation through the blood-brain barrier following (IN) administration, B IV is the AUC 0-360 (brain) following IV administration, P IV is the AUC 0-360 (blood) following IV administration, B IN is the AUC 0-360 (brain) following IN administration, P IN is the AUC 0-360 (blood) following IN administration. 45,62…”

Evaluation of Brain Targeting and Antipsychotic Activity of Nasally Administrated Ziprasidone Lipid–Polymer Hybrid Nanocarriers

“…The pharmacokinetic parameters in the plasma and brain, as the maximum drug concentration (C max ), time needed to reach C max (T max ), area under the concentration-time curve (AUC 0–8 and AUC 0–∞ ), mean residence time (MRT), elimination rate constant (K el ), and absolute bioavailability, were calculated. In addition, the direct-transport percentage (DTP%) and drug-targeting efficiency percentage (DTE%) were computed as follows: [ 63 ]. where …”