A bioanalytical UHPLC based method used for the quantification of Thymoquinone-loaded-PLGA-nanoparticles in the treatment of epilepsy

Niyaz Ahmad; Rizwan Ahmad; Sadiq Al Qatifi; Mahdi Alessa; Hassan Al Hajji; Md Sarafroz

doi:10.1186/s13065-020-0664-x

A bioanalytical UHPLC based method used for the quantification of Thymoquinone-loaded-PLGA-nanoparticles in the treatment of epilepsy

BMC Chem. 2020 Feb 14;14(1):10. doi: 10.1186/s13065-020-0664-x. eCollection 2020 Dec.

Authors

Niyaz Ahmad^{1

2}, Rizwan Ahmad³, Sadiq Al Qatifi¹, Mahdi Alessa¹, Hassan Al Hajji¹, Md Sarafroz²

Affiliations

¹ 1Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia.
² 2Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia.
³ 3Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia.

Abstract

To formulate a nanoformulation (PLGA-NPs) and to improve brain bioavailability for thymoquinone (THQ) through intranasal (i.n.) drug delivery, using a newly UHPLC-PDA developed the method and validated. Five different THQ-PLGA-NPs (THQ-N1 to THQ-N5) were prepared by emulsion solvent evaporation method. A new UHPLC method developed and validated for biodistribution studies in the rat's brain, lungs and plasma. Optimized-THQ-N1-NPs showed a particle size of 97.36 ± 2.01 nm with a low PDI value of 0.263 ± 0.004, ZP of - 17.98 ± 1.09, EE of 82.49 ± 2.38% and DL of 5.09 ± 0.13%. THQ-N1-NPs showed sustained release pattern via in vitro release profile. A bioanalytical method was developed by UHPLC-PDA and validated for the evaluation of pharmacokinetics parameters, biodistribution studies, brain drug-targeting potential (89.89 ± 9.38%), and brain-targeting efficiency (8075.00 ± 113.05%) studies through intranasal administration which showed an improved THQ-brain- bioavailability, compared to i.v. Moreover, THQ-PLGA-NPs improved the seizure threshold treatment i.e. epilepsy increasing current electroshock (ICES) rodent models induced seizures in rats. A significant role of THQ-PLGA-NPs with high brain targeting efficiency of the nanoformulations was established. The reported data supports the treatment of epilepsy.

Keywords: Brain bioavailability and pharmacokinetic; Epilepsy; PLGA-nanoparticles; Thymoquinone; UHPLC-PDA.