ESPN 54th Annual Meeting

ESPN 2022


 
Mitochondria-Targeted CoQ10 Formulation for the Treatment of CoQ10 Nephropathies
HAMIDE SENA OZBAY 1 SAMIYE YABANOGLU CIFTCI 1 IPEK BAYSAL 2 MERVE GULTEKINOGLU 3 CEMIL CAN EYLEM 4 KEZBAN ULUBAYRAM 3 EMIRHAN NEMUTLU 4 REZAN TOPALOGLU 5 FATIH OZALTIN 5

1- HACETTEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BIOCHEMISTRY, SIHHIYE, ANKARA 06100, TURKEY
2- HACETTEPE UNIVERSITY, HACETTEPE UNIVERSITY, FACULTY OF HEALTH SCIENCES, ANKARA, TURKEY
3- HACETTEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF BASIC PHARMACEUTICAL SCIENCES, SIHHIYE, ANKARA 06100, TURKEY
4- HACETTEPE UNIVERSITY, FACULTY OF PHARMACY, DEPARTMENT OF ANALYTICAL CHEMISTRY, SIHHIYE, ANKARA 06100, TURKEY
5- HACETTEPE UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF PEDIATRICS, DIVISION OF PEDIATRIC NEPHROLOGY, SIHHIYE, ANKARA 06100, TURKEY
 
Introduction:

 Coenzyme Q10 (CoQ10) deficiency causes many organ dysfunctions, with isolated kidney involvement leading to chronic kidney disease in some subtypes. Early administration of oral CoQ10 has been observed to reduce proteinuria and has been postponed the onset of chronic kidney disease in these patients, suggesting that it may have renoprotective properties. On the other hand, the limited bioavailability of CoQ10 in mitochondria is an obstacle to its effectiveness. 

Material and methods:

 We aimed to formulate mitochondria targetted CoQ10-loaded poly(lactic-co-glycolic acid)-poly(ethylene glycol)-triphenylphosphonium nanoparticles (CoQ10-TPP-NPs) that may be used to treat CoQ10 nephropathies more effectively. Their effects were evaluated on an in vitro disease model, which was created in HK-2 cell line by siRNA based silencing of the COQ8B. Mitochondrial functions were determined by metabolomic analyses.

Results:

The size of these nanoparticles was determined to be around 150 nm, with a zeta potential of +20 mV. The entrapment efficiency of the nanoparticles was found to be 40%. It was found that these nanoparticles did not show cytotoxic effects on HK-2 cells. Metabolomic analyses showed increased rate of tricarboxylic acid cycle in COQ8B-/- cells treated with CoQ10-TPP-NPs as compared to those treated with free-CoQ10 .

Conclusions:

Our mitochondria-targetted formulation was found to be more effective than free-CoQ10 in CoQ10  deficient HK-2 cells.  If its in vivo effects confirm our in vitro observations, this formulation would be a promising therapeutic option in the treatment of CoQ10 nephropathies.