Mitochondria-targeted CoQ 10 loaded PLGA-b-PEG-TPP nanoparticles: Their effects on mitochondrial functions of COQ8B -/- HK-2 cells.

Autor: Sena Ozbay H; Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, Sıhhiye, Ankara 06100, Turkey. Electronic address: senaozbay@hacettepe.edu.tr., Yabanoglu-Ciftci S; Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, Sıhhiye, Ankara 06100, Turkey. Electronic address: samiye@hacettepe.edu.tr., Baysal I; Hacettepe University, Hacettepe University, Faculty of Health Sciences, Ankara, Turkey. Electronic address: ipekbaysal@hacettepe.edu.tr., Gultekinoglu M; Hacettepe University, Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Sıhhiye, Ankara 06100, Turkey. Electronic address: merve.g@hacettepe.edu.tr., Can Eylem C; Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry, Sıhhiye, Ankara 06100, Turkey. Electronic address: cemilcaneylem@gmail.com., Ulubayram K; Hacettepe University, Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Sıhhiye, Ankara 06100, Turkey; Hacettepe University, Graduate Department of Bioengineering, Beytepe, Ankara 06800, Turkey. Electronic address: ukezban@hacettepe.edu.tr., Nemutlu E; Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry, Sıhhiye, Ankara 06100, Turkey; Hacettepe University, Faculty of Pharmacy, Bioanalytic and Omic Laboratory, Sıhhiye, Ankara 06100, Turkey. Electronic address: enemutlu@hacettepe.edu.tr., Topaloglu R; Hacettepe University, Faculty of Medicine, Department of Pediatrics, Division of Pediatric Nephrology, Sıhhiye, Ankara 06100, Turkey. Electronic address: rezantopaloglu@hacettepe.edu.tr., Ozaltin F; Hacettepe University, Faculty of Medicine, Department of Pediatrics, Division of Pediatric Nephrology, Sıhhiye, Ankara 06100, Turkey. Electronic address: fozaltin@hacettepe.edu.tr.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2022 Apr; Vol. 173, pp. 22-33. Date of Electronic Publication: 2022 Feb 26.
DOI: 10.1016/j.ejpb.2022.02.018
Abstrakt: Coenzyme Q 10 (CoQ 10 ) deficiency exhibits signs of multiple organ dysfunctions, particular subtypes present isolated kidney involvement progressing to chronic kidney disease. In these patients, early administration of oral CoQ 10 has been shown to decrease proteinuria and to delay development of chronic kidney disease, which suggests that it may have a renoprotective potential in these patients. However, CoQ 10 bioavailability in mitochondria is low, therefore its efficacy is limited. We aimed to develop mitochondria-targeted CoQ 10 loaded poly(lactic-co-glycolic acid)-poly(ethylene glycol)-triphenylphosphonium nanoparticles (CoQ 10 -TPP-NPs) that would be more efficient in the treatment of CoQ 10 nephropathies. These nanoparticles were found to have a size of approximately 150 nm and a zeta potential of + 20 mV. The entrapment efficiency of the nanoparticles was determined as 40%. Cytotoxicity studies showed no effect on the viability of the human kidney proximal tubule epithelial cells exposed to the nanoparticles. The efficacy of the formulated nanoparticles on in vitro disease model, which was developed in the human kidney proximal tubule epithelial cells by siRNA based silencing of the COQ8B, was evaluated through mitochondrial functions by means of metabolomic analyses. We showed that the treatment of COQ8B -/- cells with mitochondria-targeted nanoparticles was more effective in increasing the tricarboxylic acid cycle rate compared to free-CoQ 10 . Our formulation would be more effective in treatment of CoQ 10 -related nephropathies than conventional formulations.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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