A bioanalytical UHPLC based method used for the quantification of Thymoquinone-loaded-PLGA-nanoparticles in the treatment of epilepsy
Authors: Rizwan Ahmad
Niyaz Ahmad
Mahdi Alessa
Hassan Al Hajji
Md Sarafroz
Sadiq Al Qatifi
Journal: BMC chemistry (2020)
Discipline: CHEMISTRY
Keywords: Brain bioavailability and pharmacokinetic; Epilepsy; PLGA-nanoparticles; Thymoquinone; UHPLC-PDA.
Affiliations: 1Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia., 2Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia., 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. 

Retracted: No

PubPeer comments:
 Figure 4 https: imgur.com a jASRXa4 , 
 Fig 3.  DSC thermograms of pure THQ, PLGA, PV, physical mixtures of THQ, PLGA, PVA; and freeze-dried THQ-PLGA-NPs . I have no experience in collecting or plotting Differential scanning calorimetry thermograms. How sharp a transition can one expect to see in the energy flux as temperature is increased? ![file] , 
 Clockwise here from upper left: - Fig 7A from [Ahmad et al (2018)] .  The cumulative percentage release of Eugenol from EUG-NE as compared to pure Eugenol (reproduced as Fig. 5 in [Ahmad et al (2019)] ,  The cumulative percentage release of Eugenol from EUG ). - Fig. 2a from [Ahmad et al (2018b)] .  In vitro release profile of EUG-solution, EUG-loaded-PCL-NPs and CS-coated-EUG-loaded-PCL-NPs performed by using dialysis bag method, revealing sustained release pattern of EUG-loaded-PCL-NPs and CS-coated-EUG-loaded-PCL-NPs . - Fig. 5A from [Ahmad et al (2019a)] .  In vitro release profile of DAUNu2013S, DAUNu2013loadedu2013PLGAu2013NPs and CSu2013DAUNu2013PLGAu2013NPs performed by using dialysis bag method, revealing sustained release pattern of DAUNu2013PLGAu2013NPs, and CSu2013DAUNu2013PLGAu2013NPs . - Fig. (5)A from [Ahmad et al (2019b)] .  In vitro release profile of GRA-solution, GRA-loaded-PCL-NPs and CS-coated-GRA-loaded-PCL-NPs performed by using dialysis bag method, revealing sustained release pattern of GRA-loaded-PCL-NPs and CS-coated-GRA-loaded-PCL-NPs . - Fig 6a from [Ahmad et al (2019c)] .  The cumulative percentage release of curcumin from Cur-SNEDDS as compared to pure curcumin. - Fig 5A from [Ahmad et al (2020)] .  In vitro release profile of CTH-S, CTHu2013loadedu2013PLGAu2013NPs and Chitosan-coated-CTHu2013loadedu2013PLGAu2013NPs performed by using dialysis bag method, revealing sustained release pattern of CTHu2013loadedu2013PLGAu2013NPs and Chitosan-coated- CTHu2013loadedu2013PLGAu2013NPs (Temp was set at 37u202fu00b0C, meanu202fu00b1u202fSD, nu202f=u202f3) at pH 7.4 (reproduced as Fig 8A in [Ahmad et al (2020a)] ). - Fig 6 from [Ahmad et al (2020b)] ,  the %age-cumulative-release of 5-FU from 5-FU-NE and 5-FU-NE-Gel when it compared with pure 5-FU-S . - **Fig. 5a from [Ahmad et al (2020c)] **.  In vitro release profile of THQ-S, and THQ-loaded-PLGA-NPs performed by using dialysis bag method, revealing sustained release pattern of THQ-PLGA-NPs . ![file] All 8 superimposed: ![file] Are there any nanopreparations with **different** pharmacokinetics? I am also impressed by the similarity of the release profiles of pure Eugenol, Daunorubicin, Glycyrrhizic Acid, curcumin, catechin, 5-FU and Thymoquinone, despite their different solubilities, etc.. ,