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


Sena Ozbay H., Yabanoglu-Ciftci S., Baysal I., Gultekinoglu M., Can Eylem C., Ulubayram K., ...More

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, vol.173, pp.22-33, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 173
  • Publication Date: 2022
  • Doi Number: 10.1016/j.ejpb.2022.02.018
  • Journal Name: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.22-33
  • Keywords: Coenzyme Q(10), COQ8B, Polymeric nanoparticle, Targeting Mitochondria, Metabolomics, Treatment, ADCK4 MUTATIONS, DELIVERY, COENZYME-Q10, PATHWAYS, CANCER
  • Hacettepe University Affiliated: Yes

Abstract

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.