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<p>Type-II diabetes mellitus and insulin resistance emerged as a significant health challenge, contributing to progressive neuronal loss and memory decline. The present study focuses on developing and optimizing oleanolic acid (OA) loaded chitosan-coated nanoemulsion (CN-NE) for targeted intranasal delivery to overcome poor bioavailability and BBB permeability issues of the phytoconstituent. The optimized formulation demonstrated superior attributes for intranasal administration, exhibiting an optimum pH, droplet size, polydispersity index, surface charge, and optimal viscosity at physiological temperatures. Additionally, the formulation achieved a high cumulative release of the entrapped drug within 8&#xa0;h, along with the maximum cumulative permeation as assessed through goat nasal mucosa, indicating the greater efficacy to permeate through the nasal mucosal cells. The safety of the formulation was ensured by biocompatibility through in vitro HaCaT cell lines and ex vivo histopathological evaluation. In vivo behavioural assessments exhibited increased cognitive capabilities. At the same time, biochemical evaluations revealed higher antioxidant enzyme activities (SOD, GSH, CAT), lower malondialdehyde levels, reduced acetylcholinesterase levels, and a substantial increase in neuronal count in brain histopathological examinations. These data imply that intranasal OA-loaded CN-NE could be a safe and effective tool for alleviating insulin resistance-induced cognitive impairment and related neurodegenerations. Collectively, these findings highlight that this system may be a potential candidate for clinical translation as a targeted therapeutic approach for metabolic and neurodegenerative disorders.</p>

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Oleanolic Acid-loaded Chitosan-coated Nanoemulsion for Safe Nose-to-brain Delivery for Insulin-resistant Memory Decline

  • 期刊论文

  • 发表日期：

    2026年3月4日

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  • Pritam Kuili,
  • Varnita Karmakar,
  • Amrita Chatterjee,
  • Wei Meng Lim,
  • Bapi Gorain

摘要

Type-II diabetes mellitus and insulin resistance emerged as a significant health challenge, contributing to progressive neuronal loss and memory decline. The present study focuses on developing and optimizing oleanolic acid (OA) loaded chitosan-coated nanoemulsion (CN-NE) for targeted intranasal delivery to overcome poor bioavailability and BBB permeability issues of the phytoconstituent. The optimized formulation demonstrated superior attributes for intranasal administration, exhibiting an optimum pH, droplet size, polydispersity index, surface charge, and optimal viscosity at physiological temperatures. Additionally, the formulation achieved a high cumulative release of the entrapped drug within 8 h, along with the maximum cumulative permeation as assessed through goat nasal mucosa, indicating the greater efficacy to permeate through the nasal mucosal cells. The safety of the formulation was ensured by biocompatibility through in vitro HaCaT cell lines and ex vivo histopathological evaluation. In vivo behavioural assessments exhibited increased cognitive capabilities. At the same time, biochemical evaluations revealed higher antioxidant enzyme activities (SOD, GSH, CAT), lower malondialdehyde levels, reduced acetylcholinesterase levels, and a substantial increase in neuronal count in brain histopathological examinations. These data imply that intranasal OA-loaded CN-NE could be a safe and effective tool for alleviating insulin resistance-induced cognitive impairment and related neurodegenerations. Collectively, these findings highlight that this system may be a potential candidate for clinical translation as a targeted therapeutic approach for metabolic and neurodegenerative disorders.