IN VIVO ASSESSMENT OF TERIFLUNOMIDE SOLID LIPID NANOPARTICLES PREPARED TO TREAT MULTIPLE SCLEROSIS
DOI:
https://doi.org/10.22159/ajpcr.2026v19i6.58771Keywords:
Teriflunomide, Solid lipid nanoparticles, Intranasal delivery, Brain targeting, Multiple sclerosisAbstract
Objectives: This study aimed to evaluate the in vivo pharmacokinetic and pharmacodynamic performance of teriflunomide-loaded solid lipid nanoparticles (TFE-SLNs) administered intranasally for enhanced brain targeting in multiple sclerosis (MS), and to compare their efficacy with intravenous (IV) solid lipid nanoparticles (SLNs) and free drug suspension.
Methods: Female mice were divided into three groups receiving intranasal (IN) teriflunomide suspension, IN TFE-SLNs, and IV TFE-SLNs. Plasma and brain drug concentrations were quantified using liquid chromatography-mass spectrometry, and pharmacokinetic parameters (maximum concentration [Cmax], time to reach maximum concentration, area under the curve [AUC], and elimination rate constant) were calculated using non-compartmental analysis. Brain-targeting efficiency was assessed using drug targeting efficiency (DTE), drug targeting index (DTI), and direct transport percentage (DTP). Pharmacodynamic evaluation was conducted in a cuprizone-induced demyelination model through histopathology and immunohistochemistry (IHC).
Results: IN TFE-SLNs exhibited superior brain delivery with higher brain Cmax (750±2.20 ng/mL at 4 h) and AUC0–t (7963.1±1.39 ng·h/mL) compared to IV SLNs and free drugs. Enhanced targeting parameters (DTE 353.2%, DTP 70.3%, DTI >1) confirmed efficient nose-to-brain transport. Histological analysis showed reduced neuronal degeneration and improved myelination in the IN SLN group. IHC demonstrated decreased glial fibrillary acidic protein and macrophage antigen-3 (MAC-3) expression with restoration of proteolipid protein, indicating reduced inflammation and demyelination.
Conclusion: IN TFE-SLNs significantly improved brain bioavailability and neuroprotective efficacy, offering a promising non-invasive strategy for effective management of MS.
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