Nimodipine loaded PLGA nanoparticles: formulation optimization using factorial design, characterization and in vitro...

Area of Science:

• Nanotechnology and Materials Science
• Pharmaceutical Sciences
• Biomedical Engineering

Background:

• Cerebral vasospasm treatment typically requires prolonged intravenous Nimodipine (NIM) infusion.
• Conventional therapy necessitates continuous intravenous administration for 1-2 weeks.
• Developing a sustained-release formulation can improve patient compliance and therapeutic outcomes.

Purpose of the Study:

• To develop and optimize sustained-release Nimodipine (NIM) nanoparticles.
• To utilize biodegradable poly (lactide-co-glycolide) (PLGA) polymers (50:50 and 85:15 ratios) as carriers.
• To evaluate formulation parameters influencing nanoparticle characteristics and drug release.

Main Methods:

• Nimodipine nanoparticles were prepared using a modified precipitation method with high-pressure homogenization.
• A 3(2) factorial design optimized drug:polymer ratio and surfactant concentration (Pluronic F 127).
• Particle size, entrapment efficiency, morphology (SEM), drug state (DSC), and in vitro release kinetics were analyzed.

Main Results:

• Optimized nanoparticles exhibited spherical morphology with sizes of 131 nm (PLGA 50:50) and 196 nm (PLGA 85:15).
• High entrapment efficiencies were achieved: 96.4% (PLGA 50:50) and 94.5% (PLGA 85:15).
• In vitro release studies demonstrated sustained NIM release over 25 days, with 94.3% from PLGA (50:50) and 63.3% from PLGA (85:15), following first-order, Fickian diffusion kinetics.

Conclusions:

• Nimodipine-loaded PLGA nanoparticles show potential for sustained drug delivery.
• The developed formulation offers a viable alternative to prolonged intravenous administration for cerebral vasospasm.
• Further in vivo studies are warranted to confirm the therapeutic efficacy and safety of these nanoparticles.