Scholarlink

<p>Sleep disorders, particularly those induced by sleep deprivation, pose significant challenges to cognitive function and overall mental health. Armodafinil (ADF), an R-enantiomer of modafinil, has demonstrated efficacy in enhancing wakefulness but is limited by poor water solubility and systemic side effects. This study explores the potential of intranasal Spanlastic nanovesicles (SNVs) as a brain-targeted delivery platform for ADF. Owing to their nanoscale size and high deformability, SNVs exhibit enhanced mucosal permeation and improved brain targeting compared to conventional intranasal delivery systems. A 3³ Box-Behnken statistical design was employed to optimize ADF-SNVs based on vesicle size (VS), zeta potential (ZPOT), and entrapment efficiency (EE). The optimized ADF-SNVs exhibited a VS of 189.62&#xa0;nm, ZPOT of -37.14 mV, and EE of 82.71%. Besides, the optimized formulation exhibited controlled drug release and boosted permeation through the nasal membrane. Pharmacokinetic studies revealed significantly higher brain bioavailability of ADF following intranasal administration of ADF-SNVs thermogel, with a notable increase in the brain-to-blood concentration ratio (AUC<sub>brain</sub>/AUC<sub>blood</sub> = 0.68). Moreover, the intranasally administered ADF-SNVs thermogel demonstrated a 2.5-fold and 4.7-fold increase in brain bioavailability compared to the intravenously and intranasally administered ADF suspensions, respectively. Histopathological assessments confirmed the safety and tolerability of the formulation. These findings underscore the potential of Spanlastics-based intranasal delivery systems as an innovative, noninvasive strategy for brain-targeted drug delivery in managing sleep disorders.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Nose-to-Brain Delivery of Armodafinil Loaded Spanlastics in Situ Gel: Formulation, Statistical Optimization, and Pharmacokinetics Evaluation

  • 期刊论文

  • 发表日期：

    2025年10月28日

查看全文
  • Omnia M. Hendawy,
  • Mohammed H. Elkomy,
  • Ahmed M Abdelhaleem Ali,
  • Randa Mohammed Zaki,
  • Basmah Nasser Aldosari,
  • Adel A. Ali,
  • Sammar Fathy Elhabal,
  • Hussein M. Eid

摘要

Sleep disorders, particularly those induced by sleep deprivation, pose significant challenges to cognitive function and overall mental health. Armodafinil (ADF), an R-enantiomer of modafinil, has demonstrated efficacy in enhancing wakefulness but is limited by poor water solubility and systemic side effects. This study explores the potential of intranasal Spanlastic nanovesicles (SNVs) as a brain-targeted delivery platform for ADF. Owing to their nanoscale size and high deformability, SNVs exhibit enhanced mucosal permeation and improved brain targeting compared to conventional intranasal delivery systems. A 3³ Box-Behnken statistical design was employed to optimize ADF-SNVs based on vesicle size (VS), zeta potential (ZPOT), and entrapment efficiency (EE). The optimized ADF-SNVs exhibited a VS of 189.62 nm, ZPOT of -37.14 mV, and EE of 82.71%. Besides, the optimized formulation exhibited controlled drug release and boosted permeation through the nasal membrane. Pharmacokinetic studies revealed significantly higher brain bioavailability of ADF following intranasal administration of ADF-SNVs thermogel, with a notable increase in the brain-to-blood concentration ratio (AUCbrain/AUCblood = 0.68). Moreover, the intranasally administered ADF-SNVs thermogel demonstrated a 2.5-fold and 4.7-fold increase in brain bioavailability compared to the intravenously and intranasally administered ADF suspensions, respectively. Histopathological assessments confirmed the safety and tolerability of the formulation. These findings underscore the potential of Spanlastics-based intranasal delivery systems as an innovative, noninvasive strategy for brain-targeted drug delivery in managing sleep disorders.

Graphical Abstract