International Journal of Nanomedicine (Jul 2025)
Dynamic Nanopeptide Assemblies for Trans-Tympanic Drug Delivery
Abstract
Evan A Patel,1 Swapnil V Shah,1 Trevor A Poulson,1 H Christopher Fry,2 Ashok A Jagasia1 1Department of Otolaryngology, Head and Neck Surgery, Rush University Medical Center, Chicago, IL, 60612, USA; 2Center for Nanoscale Material, Argonne National Laboratory, Lemont, IL, 60439, USACorrespondence: Evan A Patel, Department of Otolaryngology, Head and Neck Surgery, 610 S. Maple Avenue, Suite 3700, Oak Park, IL, 60304, USA, Tel +1 630-877-7200, Email [email protected]: Otitis media is a common otolaryngologic diagnosis worldwide. Invasive methods to curtail and treat frequent occurrences are undesirable, thus necessitating the identification and production of a non-invasive approach to treating the disease. Due to tympanic membrane thickness, ototopical drug delivery is challenging. In this preliminary study, formulations integrating nanopeptides and thermoresponsive polymeric hydrogels are utilized to improve the efficiency of trans-tympanic membrane drug delivery.Methods: Peptides were synthesized using standard Fmoc (fluorenylmethoxycarbonyl protecting group) based solid state peptide synthesis on an automated peptide synthesizer. Ciprofloxacin release was simulated using multiwell microplates with porous inserts. Rate of Ciprofloxacin release was measured over a 48-hour period using a 200 uL solution of peptide fibers and Ciprofloxacin at 1 wt% each, and the labeled peptide at 0.1 wt% in PBS at pH of 7.4. The cytotoxicity of the PA (peptide amphiphile, specifically c16-AHL3K3-CO2H) micelle and fiber with and without ciprofloxacin was investigated by examining epidermal keratinocyte viability in the presence of the material at various concentrations. Laser scanning confocal microscopy was performed with excitation of the calcein dye at 485 nm and the PA-TAMRA (rhodamine labeled peptide) at 515 nm.Results: We have demonstrated the potential viability of a self-assembled peptide amphiphile hydrogel capable of transitioning from a network of 1D nanoscale fibers to 0D micelles. This dissociative mechanism of action yields a peptide that is an effective cell penetrating peptide (CPP) while temporally controlling the release of the antibiotic ciprofloxacin.Conclusion: This work highlights the potential utility of the dynamic process of an engineered peptide hydrogel capable of dissociating into CPPs capable of facilitating drug delivery across the tympanic membrane.Keywords: peptide, self-assembly, tympanic membrane, drug release, cell culture
