Adriana Trapani1, Lorenzo Guerra2, Filomena Corbo1, Stefano Castellani3, Enrico Sanna4, Loredana Capobianco5, Anna Grazia Monteduro5, Daniela Erminia Manno5, Delia Mandracchia6, Sante Di Gioia7, Massimo Conese7. 1. Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy. 2. Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari "Aldo Moro", 70125 Bari, Italy. 3. Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", 70125 Bari, Italy. 4. Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, Faculty of Biology and Pharmacy, University of Cagliari, Cittadella Universitaria, 09042 Monserrato (Cagliari), Italy. 5. Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy. 6. Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy. 7. Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
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.
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-derivedproanthocyanidins (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 neuroblastomaSH-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.
Authors: C Carbone; D Manno; A Serra; T Musumeci; V Pepe; C Tisserand; G Puglisi Journal: Colloids Surf B Biointerfaces Date: 2016-02-06 Impact factor: 5.268
Authors: S Castellani; A Trapani; A Spagnoletta; L di Toma; T Magrone; S Di Gioia; D Mandracchia; G Trapani; E Jirillo; M Conese Journal: J Transl Med Date: 2018-05-23 Impact factor: 5.531