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<p>Traumatic brain injury (TBI), defined as a disruption in normal brain function caused by external mechanical force, affects ⁓27–69&#xa0;million individuals annually worldwide. Despite its high prevalence and association with oxidative stress, neuroinflammation, and neurological deficits, no effective brain-targeted pharmacotherapy has yet been approved for TBI management. Herein, we report an intranasal (IN) candesartan-loaded mucoadhesive nanoemulsion (CND-MNE) designed to enhance nose-to-brain (N2B) delivery and therapeutic efficacy in TBI. The optimized CND-MNE exhibited a mean globule size of 20.98 ± 0.60&#xa0;nm, spherical morphology, nasal-compatible pH, favourable spreading behaviour, enhanced flux and preserved mucosal integrity. CND-MNE revealed a 2.16- and 3.09-fold enhancement in brain C<sub>max</sub> compared with IN and intravenous suspensions (CND-SUS IN and CND-SUS IV), respectively. Additionally, enhanced N2B transport was confirmed by increased drug targeting efficiency (%DTE, 1.57-fold) and direct transport percentage (1.07-fold) compared to CND-SUS IN. In vivo, CND-MNE at high and low doses (HD, LD) reduced neurological severity scores (⁓4.8-fold and 4.0-fold), improved motor coordination [*<i>P</i> &lt; 0.05 (HD)], spatial memory (****<i>P</i> &lt; 0.0001, HD and LD), and recognition memory [*<i>P</i> &lt; 0.05 (HD)] in the C57BL/6 controlled cortical impact model. Additionally, CND-MNE (HD and LD) markedly decreased brain water content (*<i>P</i> &lt; 0.05) and preserved neuronal architecture. The levels of pro-inflammatory cytokines were lower in the CND-MNE-treated group than in the group treated with IN CND-SUS, indicating reduced neuroinflammation. Collectively, these findings highlight the potential of CND-MNE as an effective non-invasive strategy for targeted brain delivery and neuroprotection in TBI.</p> Graphical abstract <p></p>

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Nose-to-brain delivery of candesartan-loaded nanoemulsion: brain biodistribution and neurobehavioral outcomes in controlled cortical impact-induced traumatic brain injury

  • 期刊论文

  • 发表日期：

    2026年7月16日

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  • Etikala Amulya,
  • Deepali Kumari,
  • Tejaswini Kolipaka,
  • Manoj P. Dandekar,
  • Saurabh Srivastava

摘要

Traumatic brain injury (TBI), defined as a disruption in normal brain function caused by external mechanical force, affects ⁓27–69 million individuals annually worldwide. Despite its high prevalence and association with oxidative stress, neuroinflammation, and neurological deficits, no effective brain-targeted pharmacotherapy has yet been approved for TBI management. Herein, we report an intranasal (IN) candesartan-loaded mucoadhesive nanoemulsion (CND-MNE) designed to enhance nose-to-brain (N2B) delivery and therapeutic efficacy in TBI. The optimized CND-MNE exhibited a mean globule size of 20.98 ± 0.60 nm, spherical morphology, nasal-compatible pH, favourable spreading behaviour, enhanced flux and preserved mucosal integrity. CND-MNE revealed a 2.16- and 3.09-fold enhancement in brain Cmax compared with IN and intravenous suspensions (CND-SUS IN and CND-SUS IV), respectively. Additionally, enhanced N2B transport was confirmed by increased drug targeting efficiency (%DTE, 1.57-fold) and direct transport percentage (1.07-fold) compared to CND-SUS IN. In vivo, CND-MNE at high and low doses (HD, LD) reduced neurological severity scores (⁓4.8-fold and 4.0-fold), improved motor coordination [*P < 0.05 (HD)], spatial memory (****P < 0.0001, HD and LD), and recognition memory [*P < 0.05 (HD)] in the C57BL/6 controlled cortical impact model. Additionally, CND-MNE (HD and LD) markedly decreased brain water content (*P < 0.05) and preserved neuronal architecture. The levels of pro-inflammatory cytokines were lower in the CND-MNE-treated group than in the group treated with IN CND-SUS, indicating reduced neuroinflammation. Collectively, these findings highlight the potential of CND-MNE as an effective non-invasive strategy for targeted brain delivery and neuroprotection in TBI.

Graphical abstract