title: Delivery of Dual Drug Loaded Lipid Based Nanoparticles across the Blood-Brain Barrier Impart Enhanced Neuroprotection in a Rotenone Induced Mouse Model of Parkinson's Disease.
abstract: Parkinson's disease (PD) is the most widespread form of dementia where there is an age related degeneration of dopaminergic neurons in the substantia nigra region of the brain. Accumulation of α-synuclein (αS) protein aggregate, mitochondrial dysfunction, oxidative stress, and neuronal cell death are the pathological hallmarks of PD. In this context, amalgamation of curcumin and piperine having profound cognitive properties, and antioxidant activity seems beneficial. However, the blood-brain barrier (BBB) is the major impediment for delivery of neurotherapeutics to the brain. The present study involves formulation of curcumin and piperine coloaded glyceryl monooleate (GMO) nanoparticles coated with various surfactants with a view to enhance the bioavailability of curcumin and penetration of both drugs to the brain tissue crossing the BBB and to enhance the anti-parkinsonism effect of both drugs in a single platform. In vitro results demonstrated augmented inhibition of αS protein into oligomers and fibrils, reduced rotenone induced toxicity, oxidative stress, and apoptosis, and activation of autophagic pathway by dual drug loaded NPs compared to native counterpart. Further, in vivo studies revealed that our formulated dual drug loaded NPs were able to cross BBB, rescued the rotenone induced motor coordination impairment, and restrained dopaminergic neuronal degeneration in a PD mouse model.
authors.affiliation: Institute of Life Sciences , Nalco Square, Bhubaneswar 751023, India.
authors.forename: Paromita
authors.initials: P
authors.lastname: Kundu
authors.affiliation: Institute of Life Sciences , Nalco Square, Bhubaneswar 751023, India.
authors.forename: Manasi
authors.initials: M
authors.lastname: Das
authors.affiliation: Department of Pathology, Shri Ramachandra Bhanj Medical College , Cuttack 753007, India.
authors.forename: Kalpalata
authors.initials: K
authors.lastname: Tripathy
authors.affiliation: Institute of Life Sciences , Nalco Square, Bhubaneswar 751023, India.
authors.forename: Sanjeeb K
authors.initials: SK
authors.lastname: Sahoo
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D052117:Benzodioxoles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability / Q000502:physiology; D003474:Curcumin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D008081:Liposomes; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D016716:PC12 Cells; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D010880:Piperidines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D066263:Protein Aggregation, Pathological / Q000188:drug therapy / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D012402:Rotenone; D013501:Surface-Active Agents; D051844:alpha-Synuclein / Q000187:drug effects / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000978:Antiparkinson Agents; D052117:Benzodioxoles; D008081:Liposomes; D018696:Neuroprotective Agents; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D013501:Surface-Active Agents; D051844:alpha-Synuclein; D012402:Rotenone; D003474:Curcumin; C008922:piperine
keywords: Parkinson’s disease; blood−brain barrier; curcumin; lipid based nanoparticles; piperine; α-synuclein