Impact of ultrasonication techniques on the preparation of novel Amiloride-nanoemulsion used for intranasal delivery in the treatment of epilepsy. (12th November 2018)

• Record Type: Journal Article
• Authors: Ahmad, Niyaz; Ahmad, Rizwan; Alam, Md Aftab; Ahmad, Farhan Jalees; Amir, Mohd
• Is Part Of: Artificial cells, nanomedicine, and biotechnology. Volume 46(2018)Supplement 3
• Page Start: S192
• Page End: S207
• Publication Date: 2018-11-12
• Subjects: Amiloride -- nanoemulsion -- epilepsy -- UPLC-ESI-Q-TOF-MS/MS -- brain bioavailability and pharmacokinetic; Artificial cells -- Periodicals; Nanotechnology -- Periodicals; Blood substitutes -- Periodicals; Tissue engineering -- Periodicals; Molecules -- Periodicals; Biotechnology -- Periodicals; 615.39
• DOI: 10.1080/21691401.2018.1489826
• Languages: English
• ISSNs: 2169-1401

Abstract

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.