Nose-to-brain delivery of dopamine to the striatum of rats using neurotransmitter-loaded solid lipid nanoparticles: an in vivo study by brain microdialysis

Jan 4, 2026Neuropharmacology

Delivery of dopamine to the brain’s movement area in rats through the nose using special nanoparticles

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Abstract

Intranasal administration of GCS-DA-SLNs at doses of 2.5 and 4 mg/kg significantly increased extracellular dopamine levels by 130 ± 38%.

The developed dopamine-loaded lipid nanoparticles are designed for better delivery to the Central Nervous System.
Glycolchitosan coating may enhance the adherence of these nanoparticles in the nasal cavity.
Microdialysis results indicate that the lower dose of 1 mg/kg increased extracellular DOPAC levels by 70 ± 3%.
Electrophysiological recordings showed that the higher dose of 4 mg/kg enhanced HCN-mediated current amplitude in striatal neurons.
Similar effects on neuronal activity were observed in vitro with dopamine and a D1 receptor agonist.

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The intranasal route is a noninvasive method of delivering therapeutic compounds to the Central Nervous System (CNS). However, challenges associated with this method include reduced drug absorption, limited administered volume, insufficient nasal permeability, and enzymatic nasal metabolism. Nanotechnology-based delivery systems are being developed to overcome these limitations and improve drug availability and therapeutic effectiveness. In this regard, we recently developed dopamine (DA)-loaded solid lipid nanoparticles (DA-SLNs) using self-emulsifying Gelucire® 50/13 to form PEGylated SLNs for intranasal administration. To enhance mucoadhesion, we coated these lipid nanoparticles with the mucoadhesive cationic polymer glycolchitosan (GCS). In the present study, we performed microdialysis and electrophysiological experiments in a male rat model to evaluate the ability of GCS-DA-SLNs, when administered intranasally, to modify striatal extracellular DA concentrations and induce changes in the functional properties of striatal neurons. The results showed that intranasal administration of GCS-DA-SLNs at DA doses of 2.5 and 4 mg/kg significantly increased the extracellular concentration of DA (+130 ± 38%) and the extracellular concentration of DOPAC (only at the lower dose of 1 mg/kg, by 70 ± 3%). Ex vivo electrophysiological recordings in striatal neurons revealed that intranasal administration of GCS-DA-SLNs, at a DA dose of 4 mg/kg, but not 2.5, mg/kg, enhanced HCN-mediated Ih current amplitude. A similar effect was also observed in vitro when striatal neurons were exposed to DA or the D1 receptor agonist SKF81297. Overall, our data underscore the significant potential of using GCS-DA-SLN nanocarriers to efficiently deliver DA and other therapeutic compounds via the nose-to-brain pathway.

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Nose-to-brain delivery of dopamine to the striatum of rats using neurotransmitter-loaded solid lipid nanoparticles: an in vivo study by brain microdialysis

Abstract

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