title: Enhanced non invasive trans-tympanic delivery of ciprofloxacin through encapsulation into nano-spanlastic vesicles: Fabrication, in-vitro characterization, and comparative ex-vivo permeation studies.
abstract: The aim of this research was to encapsulate ciprofloxacin, a broad spectrum fluoroquinolone antibiotic, into Span 60 based nano-elastic vesicles, nano-spanlastics, for accomplishing improved non invasive trans-tympanic delivery, providing means for ototopical treatment of acute otitis media (AOM). To achieve this purpose, ciprofloxacin-loaded nano-spanlastics were prepared by thin film hydration (TFH) technique, using several non-ionic edge activators (EAs) according to full factorial design (32). The investigation of the effect of formulation variables on nano-spanlastic characteristics and selection of the optimum formula were performed using Design-Expert®software. The selected formulation was also subjected to comparative ex-vivo permeation studies through tympanic membrane (TM) of rabbits. Results revealed that the optimal nano-spanlastic formulation (S-2; containing 20% Brij 35 as an EA) exhibited nano-sized spherical vesicles (287.55±9.97nm), relatively high entrapment efficiency percent (51.81±1.57%), and good physical stability after six months of storage at 4-8°C. Ex-vivo TM permeation studies demonstrated the superiority of the optimal nano-spanlastic formulation over the commercial Ciprocin®drops. However, when compared to lipid-based elastic vesicles, nano-transfersomes, nano-spanlastics exhibited lower drug permeation through the TM. Concisely, the obtained results suggested that nano-spanlastics can be promising for improving trans-tympanic delivery of ciprofloxacin.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt. Electronic address: Abdulaziz.mohsen@pharma.cu.edu.eg.
authors.forename: Abdulaziz Mohsen
authors.initials: AM
authors.lastname: Al-Mahallawi
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
authors.forename: Omneya Mohammed
authors.initials: OM
authors.lastname: Khowessah
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
authors.forename: Raguia Ali
authors.initials: RA
authors.lastname: Shoukri
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D004432:Ear, Middle; D053758:Nanoparticles; D010316:Particle Size; D010539:Permeability; D019999:Pharmaceutical Solutions; D011817:Rabbits; D012984:Software
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D019999:Pharmaceutical Solutions; D002939:Ciprofloxacin
keywords: Elastic vesicles; Hydrophilic edge activator; Span 60; Thin film hydration; Tympanic membrane permeation