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<p>Alzheimer’s disease (AD) is an incurable neurological disorder and the primary cause of dementia globally, yet therapeutic options remain limited by poor drug efficacy, low patient adherence, and the restrictive blood-brain barrier (BBB), which prevents over 98% of small molecules from reaching the brain. Piracetam (PIRA), a nootropic agent, and cannabidiol (CBD), a neuroprotective compound, have shown potential in addressing AD-related oxidative stress, inflammation, and neurotransmitter imbalance. However, both drugs exhibit short plasma half-lives, requiring frequent dosing that may reduce patient compliance. To address these challenges, we developed a sustained-release phospholipid phase-transition gel (PPTG) depot incorporating a PIRA-CBD nanoemulsion. A combination index study demonstrated potent synergy at a 1:5 CBD: PIRA ratio. Optimization of the nanoemulsion was carried out using a Box-Behnken design, which explored oil concentration (Capryol<sup>®</sup> 90), Smix (Tween 20: Cremophor ELP), and stirring speed as key variables. A mean particle size of 137.8&#xa0;nm, a PDI of 0.155, and a zeta potential of -7.587 mV were all observed in the formulation that was optimized. Upon subcutaneous injection, the PPTG showed excellent injectability and formed a stable depot in vivo, as confirmed by gamma scintigraphy. In vitro studies revealed sustained release of 90.538 ± 2.62% PIRA and 87.202 ± 2.16% CBD over 96&#xa0;h, compared to rapid release from the drug solution. This study introduces a novel phospholipid-based phase-transition gel depot incorporating PIRA-CBD nanoemulsion, which provides sustained, targeted brain delivery to enhance therapeutic efficacy and improve patient compliance in Alzheimer’s disease management.</p> Graphical Abstract <p></p>

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Development of sustained release injectable phospholipid-based phase transition gel matrixed with Piracetam and cannabidiol loaded nanoemulsion for amelioration of Alzheimer’s therapy

  • 期刊论文

  • 发表日期：

    2025年11月26日

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  • Mohd Shahrukh,
  • Mohammad Adil,
  • Nazeer Hasan,
  • Farhan Jalees Ahmad

摘要

Alzheimer’s disease (AD) is an incurable neurological disorder and the primary cause of dementia globally, yet therapeutic options remain limited by poor drug efficacy, low patient adherence, and the restrictive blood-brain barrier (BBB), which prevents over 98% of small molecules from reaching the brain. Piracetam (PIRA), a nootropic agent, and cannabidiol (CBD), a neuroprotective compound, have shown potential in addressing AD-related oxidative stress, inflammation, and neurotransmitter imbalance. However, both drugs exhibit short plasma half-lives, requiring frequent dosing that may reduce patient compliance. To address these challenges, we developed a sustained-release phospholipid phase-transition gel (PPTG) depot incorporating a PIRA-CBD nanoemulsion. A combination index study demonstrated potent synergy at a 1:5 CBD: PIRA ratio. Optimization of the nanoemulsion was carried out using a Box-Behnken design, which explored oil concentration (Capryol® 90), Smix (Tween 20: Cremophor ELP), and stirring speed as key variables. A mean particle size of 137.8 nm, a PDI of 0.155, and a zeta potential of -7.587 mV were all observed in the formulation that was optimized. Upon subcutaneous injection, the PPTG showed excellent injectability and formed a stable depot in vivo, as confirmed by gamma scintigraphy. In vitro studies revealed sustained release of 90.538 ± 2.62% PIRA and 87.202 ± 2.16% CBD over 96 h, compared to rapid release from the drug solution. This study introduces a novel phospholipid-based phase-transition gel depot incorporating PIRA-CBD nanoemulsion, which provides sustained, targeted brain delivery to enhance therapeutic efficacy and improve patient compliance in Alzheimer’s disease management.

Graphical Abstract