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Objectives <p>Depression is a widespread psychiatric condition marked by ongoing sadness, disinterest, insomnia, and thoughts of self-harm. Fluoxetine HCl (FH) is a frequently prescribed antidepressant; however, it has low oral bioavailability (28%) due to significant first-pass metabolism and has side effects such as low blood pressure, gastrointestinal discomfort, and blurred vision. This research aimed to create and assess a novel intranasal nanostructured lipid carrier (NLC) system for FH, utilizing saffron oil (SO) as a functional lipid to enhance brain delivery while minimizing systemic side effects.</p> Methods <p>FH-NLCs were prepared using the high-pressure homogenization and ultrasonication method and was optimized based on particle size, PDI, Drug loading and entrapment efficiency.</p> Results <p>The observed mean particle size of FH-NLCs is 117.3&#xa0;nm, PDI 0.219, and ZP -44.76&#xa0;mV which were ideal for nose-to-brain delivery. The optimized formulation showed high drug loading and entrapment efficiency. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) confirmed a uniform morphology, while X-ray diffraction (XRD) and differential scanning calorimetry (DSC) indicated partial amorphization of the drug within the lipid matrix. The in vitro drug release exhibited a sustained profile without burst release, adhering to Korsmeyer-Peppas kinetics, which showed non-fickian diffusion Super Case II Transport (n = 1.14). Ex vivo permeation studies on goat nasal mucosa revealed significantly enhanced nasal mucosal permeability compared to the FH solution, indicating the permeation-enhancing properties of SO. Histopathological assessments confirmed the formulation's safety for nasal application. The pharmacodynamic evaluations demonstrated a synergistic antidepressant effect between FH and SO, thereby supporting improved therapeutic efficacy.</p> Conclusion <p>The intranasal delivery of FH through SO-based NLCs offers a promising approach for direct brain targeting, potentially enhancing clinical outcomes in depression while reducing systemic side effects of FH.</p>

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Fluoxetine HCl-Loaded Nanostructured Lipid Carriers for Nose-to-Brain Delivery: Optimization and Synergistic Role of Saffron Oil

  • 期刊论文

  • 发表日期：

    2025年9月29日

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  • Avinash R. Tekade,
  • Prasad V. Kadam,
  • Manoj K. Aswar,
  • Anil B. Gaikwad,
  • Rohit B. Shinde,
  • Snehal S. Kharade

摘要

Objectives

Depression is a widespread psychiatric condition marked by ongoing sadness, disinterest, insomnia, and thoughts of self-harm. Fluoxetine HCl (FH) is a frequently prescribed antidepressant; however, it has low oral bioavailability (28%) due to significant first-pass metabolism and has side effects such as low blood pressure, gastrointestinal discomfort, and blurred vision. This research aimed to create and assess a novel intranasal nanostructured lipid carrier (NLC) system for FH, utilizing saffron oil (SO) as a functional lipid to enhance brain delivery while minimizing systemic side effects.

Methods

FH-NLCs were prepared using the high-pressure homogenization and ultrasonication method and was optimized based on particle size, PDI, Drug loading and entrapment efficiency.

Results

The observed mean particle size of FH-NLCs is 117.3 nm, PDI 0.219, and ZP -44.76 mV which were ideal for nose-to-brain delivery. The optimized formulation showed high drug loading and entrapment efficiency. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) confirmed a uniform morphology, while X-ray diffraction (XRD) and differential scanning calorimetry (DSC) indicated partial amorphization of the drug within the lipid matrix. The in vitro drug release exhibited a sustained profile without burst release, adhering to Korsmeyer-Peppas kinetics, which showed non-fickian diffusion Super Case II Transport (n = 1.14). Ex vivo permeation studies on goat nasal mucosa revealed significantly enhanced nasal mucosal permeability compared to the FH solution, indicating the permeation-enhancing properties of SO. Histopathological assessments confirmed the formulation's safety for nasal application. The pharmacodynamic evaluations demonstrated a synergistic antidepressant effect between FH and SO, thereby supporting improved therapeutic efficacy.

Conclusion

The intranasal delivery of FH through SO-based NLCs offers a promising approach for direct brain targeting, potentially enhancing clinical outcomes in depression while reducing systemic side effects of FH.