Cyto/Biocompatibility of Dopamine Combined with the Antioxidant Grape Seed-Derived Polyphenol Compounds in Solid Lipid Nanoparticles.

Adriana Trapani,Stefano Castellani,Loredana Capobianco,Filomena Corbo,Anna Grazia Monteduro,Enrico Sanna,Lorenzo Guerra,Massimo Conese,Delia Mandracchia,Daniela Erminia Manno,Sante Di Gioia

doi:10.3390/molecules26040916

Abstract

Background: The loss of nigrostriatal neurons containing dopamine (DA) together with the “mitochondrial dysfunction” in midbrain represent the two main causes related to the symptoms of Parkinson’s disease (PD). Hence, the aim of this investigation is to co-administer the missing DA and the antioxidant grape seed-derived proanthocyanidins (grape seed extract, GSE) in order to increase the levels of the neurotransmitter (which is unable to cross the Blood Brain Barrier) and reducing the oxidative stress (OS) related to PD, respectively. Methods: For this purpose, we chose Solid Lipid Nanoparticles (SLN), because they have been already proven to increase DA uptake in the brain. DA-SLN adsorbing GSE (GSE/DA-SLN) were formulated and subjected to physico-chemical characterization, and their cytocompatibility and protection against OS were examined. Results: GSE was found on SLN surface and release studies evidenced the efficiency of GSE in preventing DA autoxidation. Furthermore, SLN showed high mucoadhesive strength and were found not cytotoxic to both primary Olfactory Ensheathing and neuroblastoma SH-SY5Y cells by MTT test. Co-administration of GSE/DA-SLN and the OS-inducing neurotoxin 6-hydroxydopamine (100 μM) resulted in an increase of SH-SY5Y cell viability. Conclusions: Hence, SLN formulations containing DA and GSE may constitute interesting candidates for non-invasive nose-to-brain delivery.

Highlights

Parkinson’s disease (PD) is considered a movement disorder that affects about 1–2% of the population above 65 years with a prevalent incidence in older adults of male gender [1]
It is noteworthy that the intranasal administration route can be, sometimes, an alternative to the oral one, which matches patient compliance and the approval of the pharmaceutical industry [16]. Moving from this background, the purpose of the present work was to evaluate the potential of the nose-to-brain delivery of antioxidant agents as polyphenol compounds and the neurotransmitter DA, both co-administered in Solid Lipid Nanoparticles (SLN) intended as a novel delivery system to achieve improved therapeutic efficacy and reduced side effects in the treatment of PD
Our previous works showed that both DA and grape seed-derived extract (GSE) can be singularly encapsulated in Gelucire® 50/13 based SLN, by using the melt-emulsification method [21,22,23,25]

Summary

Introduction

Parkinson’s disease (PD) is considered a movement disorder that affects about 1–2% of the population above 65 years with a prevalent incidence in older adults of male gender [1]. In addition to the α-synuclein (and its aggregates) toxicity, increasing evidence suggests that the so-called “mitochondrial dysfunction and oxidative stress” and the “neuroinflammation” mechanisms are involved in PD pathogenesis [6,7]. The loss of nigrostriatal neurons containing dopamine (DA) together with the “mitochondrial dysfunction” in midbrain represent the two main causes related to the symptoms of Parkinson’s disease (PD). The aim of this investigation is to co-administer the missing DA and the antioxidant grape seed-derived proanthocyanidins (grape seed extract, GSE) in order to increase the levels of the neurotransmitter (which is unable to cross the Blood Brain Barrier) and reducing the oxidative stress (OS) related to PD, respectively. Co-administration of GSE/DA-SLN and the OS-inducing neurotoxin 6-hydroxydopamine (100 μM) resulted in an increase of SH-SY5Y cell viability. Conclusions: SLN formulations containing DA and GSE may constitute interesting candidates for non-invasive nose-to-brain delivery

Objectives

Methods

Results

Discussion

Conclusion