RETRACTED ARTICLE: Brain-targeted glycyrrhizic-acid-loaded surface decorated nanoparticles for treatment of cerebral ischaemia and its toxicity assessment
Authors: Niyaz Ahmad
Abeer M Al-Subaiec
Md Aftab Alam
Mohammad Ashafaq
Rehan Abdur Rub
Sonali Sharma
Rizwan Ahmad
Farhan Jalees Ahmad
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CS-PCL-NPs Brain-targeting; Glycyrrhizic acid; PK and PD; UPLC-triple-quadrupole-Qtrap-MS/MS.
Affiliations: Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia;, Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia;, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia;, Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia;, Department of Biomedical Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia;, Department of Pharmaceutics, School of Medical and Allied Sciences, Galgotias University, Gautam Budh Nagar, Greater Noida, India;, Neuroscience and Toxicology Unit, College of Pharmacy, Jazan University, Jazan, Saudi Arabia;, Nanomedicine Lab, Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India

Abstract:  Objective: Enhancement of CS-GA-PCL-NPs (Glycyrrhizic Acid-encapsulated-chitosan-coated-PCL-Nanoparticles) bioavailability in brain. Methods: Double emulsification solvent evaporation method in order to develop CS-PCL-NPs (Chitosan-coated-PCL-Nanoparticles) followed by characterization of particle size and distribution, zeta potential, encapsulation efficiency and drug release (in vitro). To determine drug-uptake and its pharmacokinetic profile in brain as well as plasma, UHPLC (triple quadrupole Q-trap) MS/MS method was developed and optimized for CS-GA-PCL-NPs as well as to follow-up examined effective role of optimized NPs in reduction of all brain injury parameters after MCAO through the grip strength, locomotor activity, inflammatory cytokines levels, measurement of infarction volume and histopathological changes in neurons with safety/toxicity after i.n. in animals. Results: The developed NPs showed an average particle size, entrapment efficiency with PDI (polydispersity index) of 201.3 ¬± 4.6 nm, 77.94 ¬± 5.01% and 0.253 ¬± 0.019, respectively. Higher mucoadhesive property for CS-GA-PCL-NPs as compared to conventional and homogenized nanoformulations was observed whereas an elution time of 0.37 min and m/z of 821.49/113.41 for GA along with an elution time of 1.94 min and m/z of 363.45/121.40 was observed for hydrocortisone i.e. Internal standard (IS). Similarly, %CV i.e. inter and intra assay i.e. 0.49-4.41%, linear dynamic range (10-2000 ng/mL) and % accuracy of 90.00-99.09% was also observed. AUC0-24 with augmented Cmax was noted (**p &lt; .01), in Wistar rat brain as compared to i.v. treated group during pharmacokinetics studies. In MCA-occluded rats, enhanced neurobehavioral activity i.e. locomotor and grip strength along with a decrease in cytokines level (TNF-Œ± and IL-1Œ≤) was observed, following i.n. administration. Conclusions: CS-coated-GA-loaded-PCL-NPs when administered i.n. enhanced the bioavailability of the drug in rat brain as compared to i.v. administration. The observation from toxicity study concludes; the developed NPS are safe and free of any health associated risk. 

Retracted: Yes

PubPeer comments:
 Several points to note about Fig 10. Beginning with the mirror symmetry of 10(c).  10(d) contains more wallpaper than I can bother to annotate.  , 
 #1 Fig 10(e). I don t think these are all compression artifacts.  Leaving 10(f) as an exercise for the reader. , 
 Fig 8. I have concerns.   , 
 #2 It may also be of interest to compare  Representative photo-micrographs showing the TS of ratsu2019 brain ... for **normal control, CS-PCL-NPs (placebo)**, CS-GA-PCL-NPs treated groups, respectively after 14 days , with Fig 11 from [Ahmad et al (2020)] :  Representative photomicrographs showing the TS of ratsu2019 brain (A, B, and C) ... for SHAM (Main control group), **NE-gel + 0.50%CS (placebo), NRG-NE-gel + 0.50%CS treated groups**, respectively after 14 days.  , 
 #1  Figure 10. Representative photo-micrographs showing the TS of ratsu2019 ... nasal mucosa ... for normal control, **CS-PCL-NPs (placebo)**, **CS-GA-PCL-NPs** treated groups, respectively after 14 days. Below, for comparison, Fig 10(E), (G) from [Ahmad et al (2014)] :  Representative photomicrographs showing the TS of rats ... nasal mucosa (**E**, F, **G** and H) for normal control, PNIPAM-NPs (placebo), CUR-PNIPAM, DMC-PNIPAM and BDMC-PNIPAM-treated groups, respectively after 14u2009days  There are only four mucosal images in Fig 10 and five treatments listed in the legend, so it is not clear which image goes with which treatment group. , 
 #4 Extending the comparisons, the present 10(d) *[middle]* and 11B from [Ahmad et al (2020)] *[right]* have much in common with *[left]* 10A from [Ahmad et al (2014)] .  , 
 10(f). Contains a number of repeated sections of wallpaper. Otherwise, considerable overlap with *[at right]* Fig 10B from [Ahmad et al (2014)] .  , 
 #7 Two more versions of the same tissue slice: Figs 9A, 9C from [Ahmad et al (2017)] .  , 
 #3 I missed a repeated area in 8(c).  , 
 Figure 1.  Mass spectrum of (a) Glycyrrhizic Acid parent ion (protonated precursor [Mu2013H]u2212 ions at m z 821.49) and (b) Glycyrrhizic Acid product ion (major fragmented product ion at m z 113.49) showing fragmentation transitions. Should one expect mass spectra from different experiments to be so similar? Here black white-reversing (a) and superimposing it on (b), so that peaks unique to (a) and (b) are white and black respectively, while areas where they are identical cancel out and become grey.  , 
 Retracted. We, the Editors and Publishers of Artificial Cells, Nanomedicine, and Biotechnology have retracted the following article: Niyaz Ahmad, Abeer M. Al-Subaie, Rizwan Ahmad, Sonali Sharma, Md Aftab Alam, Mohammad Ashafaq, Rehan Abdur Rub Farhan Jalees Ahmad (2019) Brain-targeted glycyrrhizic-acid-loaded surface decorated nanoparticles for treatment of cerebral ischaemia and its toxicity assessment. Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 475u2013490, DOI: 10.1080 21691401.2018.1561458 This article is retracted due to image manipulation as well as reuse of images from other articles by the same authors, representing results of different experiments. This includes Figure 10(d) and (e), which can also be found in: Ahmad et al. (2020). Saudi Journal of Biological Sciences, https: doi.org 10.1016 j.sjbs.2019.11.008 In addition, concerns were raised regarding the integrity of other Figures in the article, including Figures 8 and 10. When asked for an explanation, the authors were unable to provide raw data that would support the integrity of their research. As the authors were unable to provide the original images, the Editors agreed the findings of the study are no longer valid and advised for the article to be retracted. The authors do not agree with the retraction. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. https: www.tandfonline.com doi full 10.1080 21691401.2020.1842981 ,