RESUMO
AIM: This study investigated the neuroprotective effects of resveratrol (RVT)-loaded polysorbate 80 (PS80)-coated poly(lactide) nanoparticles in a mouse model of Parkinson's disease (PD), and compared these effects with those from bulk RVT. METHODS: C57BL/6 mice received for 15 days RVT intraperitoneally (nanoparticulate or non-nanoparticulate), as well as single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that damages dopaminergic neurons and induces PD-related symptoms. RESULTS: MPTP induced significant impairments on olfactory discrimination and social recognition memory, as well as caused striatal oxidative stress and reduced the expression of tyrosine hydroxylase in striatum. RVT-loaded nanoparticles (but not bulk) displayed significant neuroprotection against MPTP-induced behavioral and neurochemical changes. CONCLUSION: These results point to RVT-loaded poly(lactide)-nanoparticles coated with PS80 a promising nanomedical tool and adjuvant therapy for PD.
Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Portadores de Fármacos/química , Fármacos Neuroprotetores/administração & dosagem , Doença de Parkinson Secundária/tratamento farmacológico , Poliésteres/química , Polissorbatos/química , Estilbenos/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Corpo Estriado/fisiopatologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/uso terapêutico , Percepção Olfatória/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson Secundária/metabolismo , Doença de Parkinson Secundária/patologia , Doença de Parkinson Secundária/fisiopatologia , Resveratrol , Estilbenos/uso terapêuticoRESUMO
Poly(lactic acid) (PLA) and PLA-poly(ethylene glycol) (PLA-PEG) nanoparticles containing resveratrol (RVT) were developed, and their antioxidant activity was evaluated. An analytical method using high performance liquid chromatography (HPLC)/photodiode array (PDA) detection was also developed and validated for RVT determination in nanoparticles. The mobile phase consisted of methanol : water (51 : 49, v/v) flowed at 0.9 mL/min, and the PDA detector was set at wavelength of 306 nm. The mean diameter of the nanoparticles varied between 180 and 220 nm, and the encapsulation efficiency of RVT ranged from 60% to 88%. The nanoparticles containing RVT were evaluated for their ability to scavenge the radical (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) (ABTSâ¢âº). The profile obtained from the PLA nanoparticles containing RVT demonstrated that after 24 h, there was almost no increase in antioxidant activity, which was lower than that of the free RVT and RVT-loaded PLA-PEG nanoparticles. For PLA-PEG nanoparticles, the radical-scavenging activity of RVT was shown to increase with time, and after 48 h, it was similar to that observed with free RVT.
