NON-INVASIVE DRUG DELIVERY FOR OTITIS MEDIA TREATMENT
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Chemical permeation enhancers (CPEs) are frequently employed to improve the permeation of small-molecule drugs across epidermal barriers, for applications in (oto)topical drug delivery. CPEs encompass various classes of chemicals, including surfactants, alcohols, fatty acids, fatty acid derivatives and etc. To this end, hydrogel formulations were developed based on the thermo-responsive Poloxamer 407 (P407) polymer solutions, to contain a fatty acid methyl ester-based CPE and a fluoroquinolone antibiotic for the local treatment of otitis media. The hydrogel formulation was shown to improve the passive drug flux across the tympanic membrane in an ex vivo model and led to successful treatments of otitis media in preclinical animal models. The local delivery of antibiotics could overcome the side effects associated with systemic antibiotic exposure and lessen the development of antimicrobial resistance. Furthermore, careful structural characterization and impedance-based permeation study suggested that the CPE-drug interactions form molecular constructs which could aid in the disruption of lipid bilayer integrity. Following up on this, a library of CPEs and drugs was studied systematically for their potential molecular complexation, revealing design criteria for future (oto)topical drug formulations.