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Chemical permeation enhancers (CPEs) represent a prevalent and safe strategy to enable non-invasive drug delivery across skin-like biological barriers such as the tympanic membrane (TM). While most existing CPEs interact strongly with the lipid bilayers in the stratum corneum to create defects as diffusion paths, their interactions with the delivery system, such as polymers forming a hydrogel, could compromise gelation, formulation stability, and drug diffusion. To overcome that challenge, we explore the differing interactions present with sodium dodecyl sulfate (SDS), an ionic surfactant and a common CPE, and methyl laurate (ML), a non-ionic counterpart with a similar length alkyl chain. Notably, we show that the use of ML effectively decouples permeation enhancement from gelation, enabling sustained delivery across TMs to treat acute otitis media (AOM) that is not possible with the use of SDS. We reveal that ML and ciprofloxacin form a pseudo-surfactant that significantly boosts transtympanic permeation. The middle ear ciprofloxacin concentration is increased by 70-fold in vivo in a chinchilla AOM model, yielding superior efficacy and biocompatibility than the previous highest-performing formulation. Beyond improved efficacy and biocompatibility, this single-CPE formulation significantly accelerates its progression toward clinical deployment.


Student publication.

This is the peer reviewed version of the following article:

S. S. Liu, J. M. White, Z. Chao, R. Li, S. Wen, A. Garza, W. Tang, X. Ma, P. Chen, S. Daniel, F. S. Bates, J. Yeo, M. A. Calabrese, R. Yang, A pseudo-surfactant chemical permeation enhancer to treat otitis media via sustained transtympanic delivery of antibiotics. Adv. Healthcare Mater. 2024, 2400457. , which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

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Advanced Healthcare Materials



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