Preservation of Dopamine Levels in a Mouse Model of Parkinson's Disease by Carboxymethylated Silica and Starch Nanoparticles Coupled to Silybin

• Published in: ChemistrySelect (Weinheim) 2023-01, Vol.8 (3), p.n/a
• Main Authors: García, Esperanza, Arturo García‐De‐La‐Rosa, Luis, Fernanda Veloz‐Castillo, María, Ángel Méndez‐Rojas, Miguel, Chavarría, Anahí
• Format: Article
• Language: English
• Subjects: carboxymethylation; MPTP model; nanoparticle; neuroprotection; Parkinson's disease; silicas; silybin; starch
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202204332

Silybin has a neuroprotective effect in different models of neurodegenerative diseases as the MPTP‐induced parkinsonian model. However, silybin has poor water solubility, decreasing its efficacy when administered orally. Therefore, the search for possible vehicles or transport systems is relevant. Among the options are the drug delivery systems (DDS). In this work, we evaluated if the use of specific solvents (water or oil) or DDS [carboxymethylated silica nanoparticles (SiO2_SIL) or starch (CMS‐SIL)] would preserve the neuroprotective effect of silybin when administered orally in a Parkinson's model induced with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). C57BL/6J male mice were exposed to MPTP (30 mg/kg i.p) and, 30 minutes after, were treated with 100 mg/kg of silybin in oil or water as solvents or coupled to silica nanoparticles or carboxymethyl starch for five consecutive days. After the last administration of MPTP and silybin, striatal dopamine levels were determined on day seven. Our results showed that silybin in water as the non‐vehicle control had no protective effect in the MPTP model. Silybin in oil preserved 57 % dopamine levels in contrast to 72 % with SiO2_SIL and 50.7 % with CSM‐SIL. In conclusion, we demonstrated that silybin was effectively coupled to carboxymethylated silica nanoparticles and carboxymethylated starch‐based DDS without losing its neuroprotective effects. This work describes the preparation and characterization of carboxymethylated silica nanoparticles or carboxymethylated starch conjugated to silybin, a poorly soluble molecule with neuroprotective effects. Both silybin conjugated nanocarriers showed an improved neuroprotective effect when administered orally in a C57BL/6J male mice Parkinson's model induced with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) in comparison to other silybin delivery systems.