Development and Optimization of Intranasal Curcumin-Loaded Polymeric Nanoparticles for Targeted Brain Delivery in Alzheimer’s Disease

Abstract

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which amyloid-β pathology, tau dysregulation, oxidative stress and neuroinflammation contribute to neuronal dysfunction. Curcumin has antioxidant, anti-inflammatory and potentially anti-amyloid properties, but its development as a CNS therapeutic is constrained by poor aqueous solubility, instability, rapid metabolism and limited systemic and brain exposure. Objective: The present work describes a Quality by Design-oriented development strategy for intranasal curcumin-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles intended to improve nasal residence, controlled release and the potential for nose-to-brain delivery. Methods: Curcumin-loaded PLGA nanoparticles were conceptually optimized using polymer concentration, PVA concentration and sonication time as critical formulation/process variables. Particle size, PDI, zeta potential and entrapment efficiency were selected as principal responses, followed by solid-state characterization, in-vitro release and ex-vivo nasal permeation. Results: The illustrative optimized formulation (F8) comprised 20 mg/mL PLGA, 1.0% PVA and 4 min sonication, producing a mean particle size of 176.4 ± 5.8 nm, PDI of 0.214 ± 0.018, zeta potential of −18.7 ± 1.9 mV, entrapment efficiency of 86.8 ± 1.7% and drug loading of 7.9 ± 0.4%. The hypothetical release profile showed 79.0 ± 1.9% release at 24 h compared with 91.0 ± 1.6% for free curcumin under the same model conditions, indicating slower release from the polymeric matrix. Ex-vivo nasal permeation was also higher for nanoparticles than free curcumin in the illustrative dataset. Conclusion: The proposed PLGA nanoparticle platform demonstrates formulation-development potential for intranasal curcumin delivery. However, the results are illustrative and require experimental confirmation, followed by nasal safety, pharmacokinetic, brain-distribution and disease-model studies before any therapeutic conclusions can be drawn.