Nose to brain delivery of selegiline loaded PLGA/lipid nanoparticles: Synthesis, characterisation and brain pharmacokinetics evaluation

• Published in: Journal of drug delivery science and technology 2022-11, Vol.77, p.103923, Article 103923
• Main Authors: Raman, Subashini, Khan, Arshad Ali, Mahmood, Syed
• Format: Article
• Language: English
• Subjects: Lipid-based formulation(s); Nasal drug delivery; Parkinson's disease; Poly(lactic-co-glycolic) acid (PLGA); Selegiline
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2022.103923

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease that promotes neuronal cell death. The primary treatment strategy for Parkinson's disease involves the therapy of an MAO-B inhibitor molecule, selegiline. The present research aims to fabricate selegiline loaded polymeric (PLGA) nanoparticles (SPNPs) and selegiline loaded lipid-PLGA hybrid nanoparticles (SLPNPs) while using the single emulsion solvent evaporation method. The prepared SPNPs and SLPNPs formulations were subjected to preliminary optimisation using particle size, zeta-potential, and entrapment efficiency (EE%), and the selected formulations were subjected to further characterisation. Scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM) confirmed the particles' 2-D spherical morphology and size. ATR-FTIR was used to evaluate the physical interactions among the formulation ingredients. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies confirm that SPNPs and SLPNPs were in an amorphous state. Ex-vivo studies showed 77.56% and 80% of drug permeation in 24 h for optimised formulations of SPNPs-2 and SLPNPs-1, respectively, while pure selegiline showed 65% Permeation. In-vivo study revealed a steady and controlled release profile with a half-life of 13.5 h, and AUC0-24 was observed at 130327.56 ± 231.6 ng/ml*h for SPNPs-2. For SLPNPs-1 an immediate release was observed with a very short half-life and AUC0-24 47548.57 ± 434.8 ng/ml*h compared with pure selegiline HCl solution with 2.3 h and AUC0-24 11116.52 ± 345.7 ng/ml*h. SLPNPs-1 has a shorter half-life due to its immediate release properties with the presence of lipid. Meanwhile, SPNPs-2, which only has a polymeric layer, has a longer half-life due to its sustained release properties. Overall, SPNPs-2 and SLPNPs-1 are promising carriers for selegiline nasal uptake and increase its brain bioavailability compared to oral absorption by pure selegiline. [Display omitted] •Parkinson's disease (PD) is the second most common progressive neurodegenerative disease that promotes neuronal cell death.•Selegiline loaded polymeric (PLGA) and lipid-PLGA hybrid nanoparticles (SLPNPs) were formulated using single emulsion solvent evaporation method.•Electron microscopy (SEM) and (HRTEM) confirmed the 2-D spherical morphology and size of the vesicles.•Ex-vivo studies showed 77.56% and 80% of drug permeation in 24 h for optimised formulations of SPNP-2 and SLP