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<p>The present study focused on the development, optimization, and evaluation an Ellagic Acid (EA)-loaded liposomal in situ gel intended for targeted intranasal delivery for the treatment of Alzheimer’s disease (AD). EA, a naturally occurring polyphenolic compound, exhibits potent antioxidant, anti-inflammatory and anti-amyloidogenic activities; However, its clinical use is restricted due to poor water solubility and low oral bioavailability. To overcome these limitations, EA-loaded liposomes were formulated through the thin-film hydration method in a systematic manner optimized through a 3² factorial design, with lipid and cholesterol concentrations selected as critical formulation variables. The optimized formulation (F8) demonstrated desirable physicochemical attributes, including nanosized vesicles (100.5 ± 5.5&#xa0;nm), polydispersity index (PDI 0.243 ± 0.2), and a stable negative surface charge (-40.65 ± 1.2 mV), ensuring colloidal stability. In vitro release studies indicated sustained drug release, with 96.4 ± 2.5% release from liposomes at 12&#xa0;h, while incorporation into a thermosensitive in situ gel achieved 81.4 ± 0.06% diffusion, highlighting prolonged retention at the nasal mucosa. The developed gel exhibited favorable pharmaceutical properties, including physiological pH (6.4 ± 0.31), appropriate viscosity (770 ± 6.3cps), and excellent spreadability (24.60 ± 3.4&#xa0;g/cm/sec), supporting patient compliance and intranasal administration. In vivo pharmacodynamic evaluation in scopolamine-induced Alzheimer’s rat models revealed significant improvement in cognitive performance in the Elevated Plus Maze (14 ± 1&#xa0;s) and Novel Object Recognition tests (13 ± 1.5&#xa0;s). Treatment also restored TNF-α (185 ± 8.1 Pg/ml) and IL-6 (80 ± 6.3Pg/ml) levels toward normal values. Histopathological findings corroborated reduced amyloid burden and neuronal degeneration in the treated group. Further studies involving detailed pharmacokinetic evaluation, long-term safety assessment, and clinical validation are required to translate this intranasal liposomal in situ gel into a clinically applicable, targeted therapy for Alzheimer’s disease.</p>

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Design and Optimization of Ellagic Acid Loaded Liposomal In-Situ Gel for Targeted Therapy in Alzheimer’s Disease

  • 期刊论文

  • 发表日期：

    2026年5月2日

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  • Bhaskar Kurangi,
  • Sunil Jalalpure,
  • Soham Naik Gaonkar,
  • Rubeen Nadaf,
  • Madhuri Sankpal

摘要

The present study focused on the development, optimization, and evaluation an Ellagic Acid (EA)-loaded liposomal in situ gel intended for targeted intranasal delivery for the treatment of Alzheimer’s disease (AD). EA, a naturally occurring polyphenolic compound, exhibits potent antioxidant, anti-inflammatory and anti-amyloidogenic activities; However, its clinical use is restricted due to poor water solubility and low oral bioavailability. To overcome these limitations, EA-loaded liposomes were formulated through the thin-film hydration method in a systematic manner optimized through a 3² factorial design, with lipid and cholesterol concentrations selected as critical formulation variables. The optimized formulation (F8) demonstrated desirable physicochemical attributes, including nanosized vesicles (100.5 ± 5.5 nm), polydispersity index (PDI 0.243 ± 0.2), and a stable negative surface charge (-40.65 ± 1.2 mV), ensuring colloidal stability. In vitro release studies indicated sustained drug release, with 96.4 ± 2.5% release from liposomes at 12 h, while incorporation into a thermosensitive in situ gel achieved 81.4 ± 0.06% diffusion, highlighting prolonged retention at the nasal mucosa. The developed gel exhibited favorable pharmaceutical properties, including physiological pH (6.4 ± 0.31), appropriate viscosity (770 ± 6.3cps), and excellent spreadability (24.60 ± 3.4 g/cm/sec), supporting patient compliance and intranasal administration. In vivo pharmacodynamic evaluation in scopolamine-induced Alzheimer’s rat models revealed significant improvement in cognitive performance in the Elevated Plus Maze (14 ± 1 s) and Novel Object Recognition tests (13 ± 1.5 s). Treatment also restored TNF-α (185 ± 8.1 Pg/ml) and IL-6 (80 ± 6.3Pg/ml) levels toward normal values. Histopathological findings corroborated reduced amyloid burden and neuronal degeneration in the treated group. Further studies involving detailed pharmacokinetic evaluation, long-term safety assessment, and clinical validation are required to translate this intranasal liposomal in situ gel into a clinically applicable, targeted therapy for Alzheimer’s disease.