Nano-transfersomal ciprofloxacin loaded vesicles for non-invasive trans-tympanic ototopical delivery: In-vitro optimization, ex-vivo permeation studies, and in-vivo assessment

Ciprofloxacin is a synthetic fluoroquinolone antibiotic that has been used for systemic treatment of otitis media in adults. It was approved for topical treatment of otorrhea in children with tympanostomy tubes. The aim of this work was to enhance the local non-invasive delivery of ciprofloxacin to the middle ear across an intact tympanic membrane (TM) in an attempt to treat acute otitis media (AOM) ototopically. In order to achieve this goal, ciprofloxacin nano-transfersomal vesicles were prepared by thin film hydration (TFH) technique, using several edge activators (EAs) of varying hydrophilic-lipophilic balance (HLB) values. A full factorial design was employed for the optimization of formulation variables using Design-Expert (R) software. The optimal formulation was subjected to stability testing, ex-vivo permeation studies (through ear skin and TM of rabbits), and in-vivo evaluation. Results revealed that the optimal formulation (composed of phospholipid and sodium cholate as an EA at a molar ratio of 5:1) exhibited enhanced ex-vivo drug flux through ear skin and TM when compared with the commercial product (Ciprocin (R) drops). It demonstrated a greater extent of in-vivo drug deposition in the TM of albino rabbits relative to Ciprocin (R). Consequently, transfersomes could be promising for the non-invasive transtympanic delivery of ciprofloxacin. (C) 2014 Elsevier B.V. All rights reserved.