RETRACTED ARTICLE: Impact of ultrasonication techniques on the preparation of novel Amiloride-nanoemulsion used for intranasal delivery in the treatment of epilepsy
Authors: Md Aftab Alam
Mohd Amir
Niyaz Ahmad
Rizwan Ahmad
Farhan Jalees Ahmad
Journal: Artificial Cells Nanomedicine and Biotechnology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Amiloride; UPLC-ESI-Q-TOF-MS/MS; brain bioavailability and pharmacokinetic; epilepsy; nanoemulsion.
Affiliations: a Department of Pharmaceutics, College of Clinical Pharmacy , Imam Abdulrahman Bin Faisal University , Dammam , Kingdom of Saudi Arabia., b Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy , Imam Abdulrahman Bin Faisal University , Dammam , Kingdom of Saudi Arabia., c Department of Pharmaceutics, School of Medical and Allied Sciences , Galgotias University , Gautam Budh Nagar , Greater Noida , India., d Nanomedicine Lab , Department of Pharmaceutics, School of Pharmaceutical Education and Research , Jamia Hamdard, Hamdard Nagar , New Delhi , India.

Abstract:  Aim: To develop a nanoemulsion-nanoformulation in order to enhance brain bioavailability for Amiloride (Amilo) via intranasal (i.n.) drug delivery in the brain. Material and methods: Oleic Acid, Tween-20 and Carbitol were selected as oil, surfactant and co-surfactant, respectively. For nanoemulsion preparation, an aqueous micro titration method followed by a high energy ultra-sonication method was used whereas three-factor three-level central composite design was employed to get the best formulation. The independent variables selected for the optimization were %oil, % Surfactant and co-surfactant (Smix) and sonication time (seconds). Results: Based on the constraints applied for independent and dependent variables, the optimized formulation was selected with 2.5% oil, 10% Smix and a sonication time of 45 s. The experimental values observed for dependent variables such as hydrodynamic diameter (nm), % transmittance and % cumulative drug release were found to be 89.36 ± 11.18 nm, 99.23 ± 0.84% and 80.36 ± 5.48%, respectively. Results showed; a spherical shape (transmission electron microscopy and scanning electron microscopy - assisted morphological characterization), polydispersity index (0.231 ± 0.018), zeta potential (-9.83 ± 0.12 mV), refractive index (1.38 ± 0.042), viscosity (41 ± 5 cp), pH (6.4 ± 0.18) and drug content of 98.28 ± 0.29%, for optimized Amiloride-loaded-Nanoemulsion (Amilo-NE). For bioavailability evaluation, ultra-performance liquid chromatography-mass spectroscopy based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency (1992.67 ± 45.63%) and nose-to-brain transport (586.18 ± 11.63%) whereby an enhanced Amilo-brain bioavailability was observed as compared to intravenous administration (i.v.). Furthermore, Amilo-NE enhanced the treatment in seizure threshold i.e. both rodent models of epilepsy (increasing current electroshock and pentylenetetrazole) induced seizures in mice. Conclusion: A significant role of Amilo-NE as observed after high targeting potential and efficiency of the formulation supports the easy brain targeting for Amilo-NE. 

Retracted: Yes

PubPeer comments:
 Figure 4B,  TEM images of prepared nanoemulsion through ... **(B) ultrasonication technique** ; and 6D,  transmission electron microscopy (TEM) images [of Amilo-NE]. ![file] Fig 3A,B from [Ahmad et al (2018)] .  The EUG-NE was formulated by high pressure homogenization (HPH) and also high energy ultrasonication technique (Figure 3A and B) . ![file] Amiloride or Eugenol? , 
 Retracted [11 January 2021] . ----------------------------------------- We, the Editors and Publishers of Artificial Cells, Nanomedicine, and Biotechnology have retracted the following article: Niyaz Ahmad, Rizwan Ahmad, Md Aftab Alam, Farhan Jalees Ahmad Mohd Amir. (2018). Impact of ultrasonication techniques on the preparation of novel Amiloride-nanoemulsion used for intranasal delivery in the treatment of epilepsy. Artificial Cells, Nanomedicine, and Biotechnology, 46:sup3, S192u2013S207. DOI: 10.1080 21691401.2018.1489826 This article is retracted due to reuse of images from other articles by the same authors, representing results of different experiments. This includes a section of Figure 6(d) which can also be found in: Ahmad et al. (2018). Ultrasonication techniques used for the preparation of novel Eugenol-Nanoemulsion in the treatment of wounds healings and anti-inflammatory. Journal of Drug Delivery Science and Technology, https: doi.org 10.1016 j.jddst.2018.06.003 As well as Figure 4(b), which can also be found in: Ahmad et al. (2018). Journal of Drug Delivery Science and Technology, https: doi.org 10.1016 j.jddst.2018.06.003 In addition, concerns were raised regarding the integrity of other Figures in the article, including Figure 1. 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. ,