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    Development and in vitro evaluation of temozolomide-loaded PLGA nanoparticles in a thermoreversible hydrogel system for local administration in glioblastoma multiforme
    (Elsevier, 2020) Sayiner, Ozgun; Arisoy, Sema; Comoglu, Tansel; Ozbay, Feyza Gul; Esendagli, Gunes
    With its ability to cross the blood-brain barrier, temozolomide (TMZ) is the first-line treatment option in glioblastoma multiforme therapy. This study aims to design TMZ-loaded PLGA nanoparticles (TMZ-PLGA-NP) in a thermoreversible hydrogel system comprising Pluronic (R) F-127. TMZ-PLGA-NP were prepared via emulsion-solvent evaporation method using dimethylformamide (DMF) as organic solvent and PVA solution as stabilizer. Experimental parameters for the formulation process and in vitro release profiles of free drug, TMZ-PLGA-NP and TMZ-PLGA-NP-loaded in hydrogel were investigated. Particle size in the range of 100-200 nm with an encapsulation efficiency of 55-70% has been obtained. In vitro studies showed that the TMZ-PLGA-NP loaded in hydrogel formulations have significantly slowed down the release process, providing controlled and sustained release. These nanoparticles were efficiently taken up by the glioblastoma cells and the TMZ released from the TMZ-PLGA-NP-loaded in hydrogel could reach to the efficiency of direct exposure to the free-drug. In conclusion, the thermoreversible hydrogel system containing TMZ-loaded PLGA nanoparticles may serve as a promising approach that could sustain long-term drug release for the treatment of residual glial tumors after surgery.
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    In vitro and in vivo evaluation of levodopa-loaded nanoparticles for nose to brain delivery
    (Taylor & Francis Ltd, 2020) Arisoy, Sema; Sayiner, Ozgun; Comoglu, Tansel; Onal, Deniz; Atalay, Ozbeyen; Pehlivanoglu, Bilge
    Parkinson's disease (PD) is a neurodegenerative disease which is characterized by the loss of dopaminergic neurons in the brain. Levodopa is the drug of choice in the treatment of PD but it exhibits low oral bioavailability (30%) and very low brain uptake due to its extensive metabolism by aromatic amino acid decarboxylase in the peripheral circulation. Moreover, levodopa has psychic, gastrointestinal, and cardiovascular side effects, and most importantly, short and frequent stimulation of dopamine receptors lead to undesirable conditions such as dyskinesia over time. The challenges are to increase the therapeutic efficiency, the bioavailability and decreasing the unfavourable side effects of levodopa. Biocompatible nano-sized drug carriers could address these challenges at molecular level. For this purpose, levodopa-loaded Poly (lactide-co-glycolide) acid nanoparticles were prepared by double emulsion-solvent evaporation method for nose to brain drug delivery. Parameters such as homogenization speed, and external and internal phase content were modified to reach the highest loading efficiency. F1-1 coded formulation showed prolonged release up to 9 h. Carbodiimide method was used for surface modification studies of nanoparticles. The efficacy of the selected nanoparticle formulation has been demonstrated by in vivo experiments in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced PD model in mice.