Introduction: Intranasal delivery of insulin offers a promising non-invasive route to target the brain, particularly for neurodegenerative disorders like Alzheimer’s disease (AD). However, challenges such as enzymatic degradation in the nasal cavity and limited mucosal absorption hinder therapeutic efficiency. This study aimed to develop and char-acterize chitosan-coated Polyethylene Glycol - Poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles to enhance insulin delivery to the brain. Materials and Methods: PEG-PLGA copolymers were synthesized and confirmed using ¹HNMR spectroscopy. Insulin-loaded nanoparticles were prepared via the nanoprecipitation method and coated with chitosan to improve mucoadhesion. Formulations were optimized based on polymer- to-surfactant ratio, surfactant type, and drug concentration. Nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and zeta potential analysis. In vitro drug release was evaluated in phosphate buffer (pH 7. 4) over 48 hours. Cytotoxicity was assessed using MTT assays on human nasal epithelial cells. results: The optimized PEG-PLGA: Tween-80 formulation (30: 100) showed the highest entrapment efficiency (61. 4 ± 2. 38%), optimal particle size (182. 2 ± 5. 98 nm), and stable zeta potential (–9. 08 ± 0. 09 mV). Chitosan-coated nanoparticles demonstrated sustained insulin release over 48 hours, with reduced burst effect compared to uncoated or PVA-based formulations. TEM confirmed spherical morphology with smooth surfaces. In vitro cell viability exceeded 90 Results: The optimized PEG-PLGA: Tween-80 formulation (30: 100) showed the highest entrapment efficiency (61. 4 ± 2. 38%), optimal particle size (182. 2 ± 5. 98 nm), and stable zeta potential (-9. 08 ± 0. 09 mV). Chitosan-coated nanoparticles demonstrated sustained insulin release over 48 hours, with reduced burst effect compared to uncoated or PVA-based formulations. TEM confirmed spherical morphology with smooth surfaces. In vitro cell viability ex-ceeded 90% across all formulations at concentrations up to 200 μg/mL, indicating good biocompatibility. Discussion: PEGylation and chitosan coating synergistically enhanced nanoparticle stability, drug encapsulation, and release control. Tween-80, due to its optimal hydrophilic-lipophilic balance, significantly improved entrapment and minimized early drug diffusion. The PEG shell provided steric hindrance, contributing to prolonged release, while chitosan further delayed release kinetics. These features collectively support enhanced delivery of insulin to the brain through the nasal route. Conclusion: Cervical carotid stenosis severity alone does not predict functional compromise. Integrating VEP assessment with metabolic profiling-particularly HDL and HbA1c levels-may enhance risk stratification, offering a more comprehensive and individualized evaluation, especially in asymptomatic patients. This novel perspective links biochemical markers to electrophysiological integrity and collateral efficiency in ICA stenosis. Chitosan-coated PEG-PLGA nanoparticles, especially with Tween-80, provide a safe and effective platform for intranasal insulin delivery. The optimized formulation improves drug bioavailability and enables sustained release.
Mishra et al. (Mon,) studied this question.