Otitis Media
Middle ear diseases such as otitis media (OM) affect millions worldwide, with OM being the second most common pediatric diagnosis in the U.S., leading to significant healthcare burdens, including hearing impairment, surgical interventions, and frequent antibiotic prescriptions. Traditional treatment approaches involve systemic drug administration, which often results in non-specific biodistribution and the need for higher doses, increasing the risk of side effects. Localized delivery methods, such as intratympanic injections and tympanostomy tube placement, while effective, are invasive and carry associated risks, particularly in pediatric populations.
The TM, a lipid-rich, multilayered barrier, poses challenges for drug delivery. Recently, nanoparticle-based systems have emerged as promising solutions for targeted and non-invasive drug delivery. Liposomes, particularly transfersomes, offer an advantage due to their biocompatibility, biodegradability, and ability to traverse lipid-rich biological barriers like the TM. Transfersomes, enhanced with surfactants, exhibit increased deformability, allowing them to pass through channels significantly smaller than their diameter, making them ideal candidates for trans-TM drug delivery.
Topical Drug Delivery across the Ear Drum
We describe a novel method for topical drug delivery to the middle and inner ear using liposomal nanoparticles, enabling trans-tympanic membrane (TM) drug transport without compromising its integrity. This approach represents a non-invasive alternative to trans-tympanic injections, tympanostomy tube placement, and systemic drug administration, addressing common limitations associated with these methods. Our study focuses on transfersomes (TLipo), a subclass of liposomal nanoparticles, as drug delivery vesicles designed for high penetration efficiency, specificity, and prolonged retention time in the middle and inner ear.
The TLipo nanoparticles are applied topically to the ear canal and demonstrated the ability to cross the TM within 3 hours, with their presence detected in the middle ear at 6 hours and in the inner ear at 24 hours post-administration. Comprehensive safety evaluations included in vitro cytotoxicity and in vivo ototoxicity assessments. Cell viability assays revealed no significant differences between TLipo-treated and control samples, and auditory brainstem response (ABR) testing showed no evidence of hearing loss up to one month post-administration. Immunohistochemistry confirmed the absence of hair cell loss in the cochlea at one month, highlighting the safety of this delivery system.
Confocal images of eardrum and middle ear for control (only PBS buffer), RhB, and TLipo-RhB penetration at different time points
Development of Instrumentation for Diagnosis of Otitis Media
We have developed a Shortwave Infrared (SWIR) Otoscope designed to detect middle ear fluid leverages the strong water absorption peak at the 1450 nm wavelength, combined with the increased depth of penetration offered by SWIR imaging, to provide a highly sensitive and non-invasive diagnostic tool for otitis media. SWIR light can penetrate deeper into biological tissues compared to visible or near-infrared light, allowing it to assess the tympanic membrane and detect fluid in the middle ear with greater accuracy. At 1450 nm, the absorption properties of water provide a distinct contrast between air-filled and fluid-filled cavities, enabling real-time, objective diagnosis of effusions while differentiating serous, mucoid, or purulent fluid types. The device offers improved visualization of middle ear structures, facilitating earlier and more precise diagnosis compared to traditional otoscopy. By combining high-resolution imaging with portable and user-friendly design, the SWIR otoscope reduces diagnostic uncertainty, potentially lowering unnecessary antibiotic use and surgical interventions, while enhancing clinical decision-making in both pediatric and adult populations.
Differentiation of Viral vs Bacterial Otitis Media
Our research focuses on developing advanced imaging techniques using Shortwave Infrared (SWIR) to improve the detection and diagnosis of otitis media. By leveraging SWIR's deeper tissue penetration, we aim to visualize fluid in the middle ear, a key indicator of infection. Additionally, we employ maltotriose as a potential marker for bacterial infection, given its specificity for bacterial cell walls, and indocyanine green (ICG) fluorescence to help differentiate bacterial from viral causes of infection. This approach promises to enhance diagnostic accuracy, enabling targeted treatment and reducing unnecessary antibiotic use in pediatric patients.
