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pH Gradient-Driven Loading of Doxorubicin into Niosomes: A Comparative Study Using Bromocresol Green as a Visual
Mohammed Altaee1, Ahmed Mostafa Faheem1,2, Amal Ali Elkordy1
1School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland SR1 3SD, UK.
Pharmaceutics
|July 30, 2025
Summary
This study demonstrates that Solutol HS-15 effectively stabilizes niosomes, enabling pH gradient drug loading. Bromocresol green (BCG) was used to visualize pH gradients and optimize niosomal formulations for active drug encapsulation.
Area of Science:
- Nanotechnology
- Pharmaceutical Sciences
- Drug Delivery
Background:
- Active drug loading into liposomes via pH gradients is established, but underexplored in niosomes.
- Niosomes offer a promising alternative for drug encapsulation and delivery.
- Investigating co-surfactants is key to enabling pH gradient formation in niosomes.
Purpose of the Study:
- To evaluate the impact of co-surfactants (Cremophor RH 40, ELP, Solutol HS-15) on niosomal membrane stability for pH gradient creation.
- To utilize bromocresol green (BCG) as a model molecule for visualizing and optimizing pH gradient-based active drug loading into niosomes.
- To encapsulate the therapeutic drug doxorubicin into optimized niosomal formulations using the pH gradient technique.
Main Methods:
- Niosomes were prepared using thin-film hydration with Span 60 and cholesterol, with or without co-surfactants.
- Bromocresol green (BCG) was encapsulated to visualize pH gradients, with formulations adjusted using buffers (Trizma, HEPES) and pH modifiers (HCl, citric acid).
- Doxorubicin was loaded into optimized niosomes using an ammonium sulfate gradient and Sephadex G50 gel filtration.
Main Results:
- Niosomes without co-surfactants failed to form pH gradients at acidic pH.
- All tested co-surfactants (Cremophor RH 40, ELP, Solutol HS-15) stabilized niosomes and enabled pH gradient formation.
- Solutol HS-15 formulations achieved significantly higher BCG entrapment efficiency (67.86%) compared to others, with optimized conditions yielding 68.28% doxorubicin entrapment.
Conclusions:
- Niosomal formulations incorporating Solutol HS-15 show significant potential for efficient remote drug loading.
- The use of bromocresol green (BCG) proved to be a successful novel method for assessing pH gradients and drug loading in niosomes.
- This research paves the way for developing advanced niosomal drug delivery systems utilizing active loading techniques.
