RETRACTED ARTICLE: PNIPAM nanoparticles for targeted and enhanced nose-to-brain delivery of curcuminoids: UPLC/ESI-Q-ToF-MS/MS-based pharmacokinetics and pharmacodynamic evaluation in cerebral ischemia model
Authors: Mohd Samim
Niyaz Ahmad
Iqbal Ahmad
Zeenat Iqbal
Sadiq Umar
Farhan Jalees Ahmad
Journal: Drug Delivery (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Bisdemethoxycurcumin; brain drug-targeting potential; brain-targeting efficiency; curcumin; demethoxycurcumin
Affiliations: a Nanoformulation Research Lab, Department of Pharmaceutics, Faculty of Pharmacy., b UPLC-MS Lab, Department of Pharmaceutics, Faculty of Pharmacy., c Department of Medical Elemental and Toxicology, Faculty of Science , and., d Department of Chemistry, Faculty of Science , Hamdard University , New Delhi , India.

Abstract:  Stroke is a one of the leading causes of disease and deaths worldwide, which causes irreversible deterioration of the central nervous system. Curcuminoids are reported to have a potential role in the amelioration of cerebral ischemia but they exhibit low serum and tissue levels due to low solubility and poor absorption. Curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)-loaded PNIPAM nanoparticles (NPs) were prepared by free radical polymerization and characterized for particles size, entrapment efficiency, zeta potential, in vitro release and ex vivo permeation study. Optimized CUR, DMC and BDMC-loaded NPs had the mean size of 92.46 ± 2.8, 91.23 ± 4.2 and 94.28 ± 1.91 nm; zeta potential of -16.2 ± 1.42, -15.6 ± 1.33 and -16.6 ± 1.21 mV; loading capacity of 39.31 ± 3.7, 38.91 ± 3.6 and 40.61 ± 3.6% and entrapment efficiency of 84.63 ± 4.2, 84.71 ± 3.99 and 85.73 ± 4.31%, respectively. Ultra-performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectroscopy based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency and brain drug-targeting potential studies post-intranasal (i.n.) administration which showed enhanced bioavailability of curcuminoids in brain as compared to intravenous administration. Improved neurobehavioural activity (locomotor and grip strength) and reduced cytokines levels (TNF-α and IL-1β) was observed in middle cerebral artery occlusion induced cerebral ischemic rats after i.n. administration of curcuminoids NPs. Finally, the toxicity study was performed which revealed safe nature of developed NPs. 

Retracted: Yes

PubPeer comments:
  Figure 10. Representative photomicrographs showing the TS of rats brain (A, B, C and D) and 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. With only four rows in the Figure -- A to D, E to G -- and five treatment groups itemised, it is not clear which group goes with which image. Below: Fig 10(E), (G). Above for comparison. Figure 10 from [Ahmad et al (2019)] :  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. ![file] , 
 Fig 10(A), with boosted contrast. The right-hand strip contains several kinds of mismatched wallpaper. ![file] , 
 The present Fig 10A has much in common with 10D from [Ahmad et al (2019)] and 11B from [Ahmad et al (2020)] . ![file] , 
 #3 It is a common lining which is present in all the photomicrographs. But it was performed on different studies. , 
 #1 Figure 10. Representative photomicrographs showing the TS of ratsu2019 brain (A, B, C and D) and nasal mucosa (E, F, G and H) for normal control, PNIPAM-NPs (placebo), CURPNIPAM, and DMC-PNIPAM-treated groups, respectively after 14 days. In the figure caption 10, this group (BDMCPNIPAM) is mentioned here by mistake. It was typographical error. , 
 #2 This image was provided by technician. , 
 *[at right]* Fig 10B. Considerable overlap with *[at left]* 10(f) from [Ahmad et al (2019)] . 10(f) itself contains a number of repeated sections of wallpaper. ![] , 
 #7 Two more versions of the same tissue slice: Figs 9A, 9C from [Ahmad et al (2017)] . ![] , 
 #1  Figure 10. 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. Overlap between both (E) and (G), and (H). In addition, (H) displays some internal repetitions. ![file] , 
 Figure 1.  Comparative ... TEM images of (D) PNIPAM-CUR, (E) PNIPAM-DMC... ![file] Unexpected overlap. Below: Figure 1. TEM image of (E) PNIPAM-DMC. Above: Figure 1 from [Ahmad et al (2018)] ,  ... transmission electron microscopy (TEM) (D) images of quercetin mucoadhesive nanoemulsion. ![file] Surprising overlap (after rotation and rescaling). , 
 #10 Overlap maybe not quite so surprising given the later appearance of *[left]* Fig 6 in [Ahmad et al (2017)] ,  Transmission electron microscopy (TEM) image of SNEDDS with a Qur of optimized Qur-SNEDDS. ![] Also of interest, Fig 1 (A-C),  Comparative SEM images of *(A) PNIPAM-CUR*, **(B) PNIPAM-DMC** and *(C) PNIPAM-BDMC* . Here at left. Unexpected overlap between panels A and C. ![file] Alse, B appears to match Fig 10(c) from [Ahmad et al (2017n)] ,  Comparative SEM ...images of (a) Cur-CS-NPs, (b) DMC-CS-NPs, and **(c) BDMC-CS-NPs** . Here at right. , 
 Retracted [20 January 2021] . ------------------------------------------ We, the Editors and Publishers of Drug Delivery, have retracted the following article: Niyaz Ahmad, Iqbal Ahmad, Sadiq Umar, Zeenat Iqbal, Mohd Samim Farhan Jalees Ahmad (2016) PNIPAM nanoparticles for targeted and enhanced nose-to-brain delivery of curcuminoids: UPLC ESI-Q-ToF-MS MS-based pharmacokinetics and pharmacodynamic evaluation in cerebral ischemia model, Drug Delivery, 23:7, DOI: 10.3109 10717544.2014.941076 This article is retracted due to reuse of images from other articles by the same authors, representing results of different experiments. This includes Figure 1(B), which can also be found in the following article, where itu2019s presented, after contrast and frame adjustments, as Figure 10(c): Ahmad et al. (2017) Isolation, characterization, and quantification of curcuminoids and their comparative effects in cerebral ischemia, Journal of Liquid Chromatography Related Technologies, DOI: 10.1080 10826076.2017.1293549 In addition, various panels from Figure 10 were reused in other articles, after color adjustments, as follows: Figure 10(a) is presented as Figure 10(d) in: Ahmad et al. (2019), Brain-targeted glycyrrhizic-acid-loaded surface decorated nanoparticles for treatment of cerebral ischemia and its toxicity assessment, Artificial Cells and Nanotechnology, DOI: 10.1080 21691401.2018.1561458 Figure 10(a) is presented as Figure 11(b) in: Ahmad et al (2020), Poloxamer-chitosan-based Naringenin nanoformulation used in brain targeting for the treatment of cerebral ischemia, Saudi Journal of Biological Sciences, DOI: 10.1016 j.sjbs.2019.11.008 Figure 10(b) is presented as Figure 10(f) in: Ahmad et al. (2019), Brain-targeted glycyrrhizic-acid-loaded surface decorated nanoparticles for treatment of cerebral ischemia and its toxicity assessment, Artificial Cells and Nanotechnology, DOI: 10.1080 21691401.2018.1561458 Figure 10(e) is presented as Figure 10(b), and an excerpt of Figure 10(g) is presented as one of the mirror-image sides of Figure 10(c) in: Ahmad et al. (2019), Brain-targeted glycyrrhizic-acid-loaded surface decorated nanoparticles for treatment of cerebral ischemia and its toxicity assessment, Artificial Cells and Nanotechnology, DOI: 10.1080 21691401.2018.1561458 The authors have not responded to our requests to provide an explanation or to provide the original images. Because of this, the editor agreed the findings of the study are no longer valid and advised for the article to be retracted. 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. ,