Design and Optimization of Agmatine Sulphate Loaded Solid Lipid Nanoparticles for Neurological Disorders: A DOE Approach

Objectives

This study focuses on the formulation and optimization of Solid Lipid Nanoparticles (SLNs) containing agmatine sulfate, with the goal of enhancing its bioavailability and minimizing rapid metabolic degradation, thereby improving its therapeutic application in neurological conditions.

Materials and Methods

Solid Lipid Nanoparticles (SLNs) containing agmatine sulfate were formulated using the hot melt homogenization method. Glyceryl Monostearate (GMS) served as the lipid matrix, while Tween 80 and Span 80 were employed as surfactants. A Box-Behnken Design (BBD) was utilized to systematically assess the impact of three independent variables-concentrations of GMS, Tween 80, and Span 80-on critical formulation parameters: particle size, Polydispersity Index (PDI), and entrapment efficiency. The optimized formulation was thoroughly characterized using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), particle size analysis, and in vitro drug release profiling.

Results

The optimized SLN formulation exhibited a mean particle size of 130.5 nm, a PDI of 0.189, and an entrapment efficiency of 95%. Compatibility studies confirmed the absence of significant interactions between agmatine sulfate and formulation excipients, verifying successful encapsulation within the lipid matrix. In vitro drug release displayed a biphasic profile characterized by an initial burst followed by sustained release over 24 hr. Kinetic modeling revealed a strong fit with the Higuchi model (R²=0.9644), indicating diffusion-controlled drug release.

Conclusion

The developed agmatine sulfate-loaded SLNs exhibit favorable properties for targeted brain delivery and prolonged release, highlighting their potential utility in the treatment of neurological disorders. This formulation strategy could substantially enhance the clinical performance of agmatine by improving both its bioavailability and therapeutic effectiveness.