Primjena nanočestica zlata i selena za poboljšanje terapije L-dopom u liječenju Parkinsonove bolesti kod Wistar štakora

master's thesis

• Title (english): Application of gold and selenium nanoparticles for improving L-dopa therapy for Parkinson's disease in Wistar rat
• Author: Manuela Oroz
• Mentor: Ivana Vinković Vrček (mentor)
• Mentor: Domagoj Đikić (komentor)
• Committee member: Domagoj Đikić (predsjednik povjerenstva)
• Committee member: Romana Gračan (član povjerenstva)
• Committee member: Petra Peharec Štefanić (član povjerenstva)
• Committee member: Vesna Benković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-01-11, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Parkinsonova bolest druga je najčešća neurodegenerativna bolest koju karakterizira propadanje dopaminergičnih neurona u supstanciji nigri i, posljedično, manjak dopamina. Terapijski pristupi uglavnom su usmjereni na motoričke simptome i nažalost gube svoju učinkovitost kako neurodegeneracija i simptomi napreduju. Levodopa je trenutačni zlatni standard za liječenje Parkinsonove bolesti, no dugoročna primjena rezultira različitim nuspojavama. Liječenje neurodegenerativnih poremećaja još uvijek predstavlja veliki izazov zbog postojanja krvno-moždane barijere koja otežava efikasnu isporuku lijeka u mozak. Nanotehnologija nudi mogućnosti za poboljšanje terapijskih pristupa zbog sposobnosti nanomaterijala da budu nosači lijekova, da prolaze kroz krvno-moždanu barijeru, poboljšaju farmakološka svojstva i sigurnost lijekova te isporuče lijekove na ciljano mjesto. Nanočestice selena stabilizirane polivinilpirolidonom i nanočestice zlata stabilizirane peptidoglikanskim monomerom ispitane su kao nosači za isporuku levodope s ciljem postizanja neuroprotektivnog učinka. Određivana je njihova sposobnost smanjenja oksidativnog stresa uzrokovanog levodopom u in vivo modelu Parkinsonove bolesti. Štakori oba spola su podijeljeni u 7 skupina i tretirani testnim tvarima tijekom 28 dana. Raspodjela po skupinama bila je nasumična. Oksidativni stres istražen je mjerenjem reaktivnih kisikovih vrsta i koncentracije glutationa u mozgu, bubregu, jetri i serumu tretiranih i netretiranih štakora. Rezultati upućuju na neuroprotektivno djelovanje nanočestica selena. Nanočestice zlata ne pružaju za

Abstract (english)

Parkinson’s disease is the second most common neurodegenerative disease characterized by deteriorating of dopaminergic neurons in the substance of nigra and, consequently, lack of dopamine. Present therapies are focused on reduction of motoric symptoms and sadly lose their efficiency as the neurodegeneration and symtpoms progress. Levodopa is currently a gold standard for curing Parkinson’s disease, but long-term application results in various side effects. Curing neurodegenerative disorders is still a major challenge because of existing blood-brain barrier that complicates efficient transmission of medication into the brain. Nanomaterials have a potential to upgrade therapeutic approaches because of their ability to pass through the blood-brain barrier, to improve pharmacological profile and safety of drugs and to transport drugs to the targeted area. Selenium nanoparticles stabilized by polyvinylpyrrolidone and gold nanoparticles stabilized by peptidoglycan monomer are examined as carriers for the levodopa transmission, with the goal of achieving the neuroprotective effect. Their ability to reduce oxidative stress caused by levodopa is evaluated in an in vivo model of Parkinson’s disease. Rats of both sexes were distributed in 7 groups and tested with test subtances for 28 days. The distribution of animals to the groups was random. Oxidative stress is examined by measuring reactive oxygen species and concentration of glutathione in brain, kidney, liver and serum of non-treated and treated rats. Results indicate a neuroprotective impact of selenium nanoparticles. Gold nanoparticles did not provide protective effect and it is possible that their application has a negative toxicological effects.

• Keywords: oksidativni stres; isporuka lijekova; neuroprotekcija
• Keywords (english): oxidative stress; drug delivery; neuroprotection
• Language: croatian
• URN:NBN: urn:nbn:hr:217:213285
• Project: Number: PZS-2019-02-4323; Title: Siguran pristup za razvoj nano-sustava za ciljanu isporuku lijekova u mozak; Title: Safe-by-Design Approach for Development of Nano-Enabled-Delivery Systems to Target the Brain; Acronym: SENDER; Leader: Ivana Vinković Vrček; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: PZS
• Study programme: Title: Experimental Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra eksperimentalne biologije (sveučilišni/a magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2026-01-11
• Created on: 2024-01-18 11:59:30