Engineered lecithin-based proniosomes for enhanced trans-tympanic permeation: In vitro, microbiological, ex vivo and invivo evaluation

Abstract

Otitismedia is an acute illness that specifically targets the middle ear. It affects around one-third of the pediatric population in the US. This study aimed to develop lecithin-based proniosomes to enhance the trans-tympanic permeation of the antimicrobial drug ofloxacin (OFX) and boost its antibacterial properties. Proniosomes were fabricated by the coacervation technique using a Box-Behnken design. The investigated factors were cholesterol amount (A), surfactant-to-drug ratio (B), and Brij percentage (C). The numerical optimization feature of Design-Expert® software was implemented to choose the optimum formula. The criteria for selection involved decreasing the polydispersity index (PDI) and particle size (PS) while maximizing the absolute value of zeta potential (ZP) and the percentage of entrapment efficacy (EE%). The formula with the highest desirability value (0.748), an EE% of 73.38 %, a PS of 625.35 nm, and a ZP of −44.20 mV was selected as the optimum formula. Additional investigations were conducted to illustrate the morphological appearance, release rate, stability, activity, and tolerability of the selected formula, such as invitro,ex vivo, microbiological, and invivo tests. Results demonstrated that, compared to the OFX solution (2118.72 μg/cm2), the optimum formula was found to have better otic tolerance, augmented trans-tympanic permeation (3701.01 μg/cm2), and improved antibacterial activity. The aforementioned outcomes highlighted the capability of the OFX-loaded lecithin-based proniosomes to be used as a promising non-invasive delivery system for the treatment of otitismedia.