From bench to biology: Unraveling the efficiency of novel brijosomes for trans-tympanic drug delivery

Abstract

Acute otitis media (AOM) is a prevalent middle ear infection, affecting nearly one-third of children in the U.S. This study focused on enhancing non-invasive trans-tympanic delivery of ciprofloxacin (CFX) by encapsulating it within Brijosomes, a novel nano-vesicular system for improved ototopical treatment. Brijosomes were formulated using the ethanol injection technique and optimized through a 2³ full factorial design, investigating the effects of surfactant: limonene ratio, cholesterol: drug ratio, and Brij 92 concentration. Key parameters evaluated included entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimized formulation, selected via Design Expert® software, demonstrated a high desirability value of 0.979, with EE% of 91.68 %, PS of 196.85 nm, and ZP of −25.45 mV. Characterization studies revealed that the optimized Brijosomal formula had a spherical morphology, exhibited a bi-phasic in vitro release profile, and remained stable for three months at 5 ± 3 °C. Ex vivo permeation studies demonstrated superior penetration and flux compared to CFX solution, with a 2.15-fold enhancement ratio. Microbiological assessments confirmed improved antibacterial and antibiofilm activities of the optimized formulation. Additionally, confocal laser scanning microscopy (CLSM) validated deeper penetration, consistent with the ex vivo findings. Histopathological examination confirmed the formulation's safety for ototopical application. These findings collectively emphasize the potential of CFX-loaded Brijosomes as an effective, non-invasive drug delivery system for AOM treatment.