Thermo-sensitive penetration-enhancing formulations for trans-tympanic and transdermal drug delivery
Background
Acute otitis media is one of the most common childhood diseases in the United States and present treatment of ear infections consists of systemic oral antibiotics, however these present many issues including antibiotic resistance and gastrointestinal side effects which may lower patient compliance. Local, sustained delivery of active therapeutics could allow for much higher concentrations of the drug in the middle ear than from systemic administration while minimizing systemic exposure and its adverse effects. However, the tympanic membrane (TM) presents a barrier that is largely impermeable to all but the smallest, moderately hydrophobic molecules. Therefore, the treatment of ear diseases, such as middle ear infections, suggests the need for a new composition delivery system with treatment that is noninvasive and direct acting.
Technology Overview
Boston Children’s Hospital researchers have combined therapeutic agents, permeation enhancers, and matrix-forming agents to craft compositions that, under appropriate conditions, transform into a hydrogel. Hydrogels absorb drugs and small molecules and gradually release them into the adjacent tissues. This controlled drug release results in a concentrated effect over an extended timeframe. Additionally, hydrogels are capable of adapting to and adhering to the contours of the applied surface, demonstrating compatibility with biological systems.
However, permeation enhancers, which are essential for transporting drugs across the tympanic membrane have their own challenges. Unfortunately, these enhancers hinder the gelation process of FDA-approved polymers with a reverse thermal gelation property. To overcome this, the team induced an FDA-approved polymer called P188, which does not gel at temperatures in the physiological range, to gel at below body temperature. This approach is a promising potential treatment of otitis media caused by various pathogens like H. influenzae, S. pneumoniae, or M. catarrhalis infections.
Applications
- Local therapy for otitis media to address the issue of compliance and minimize systemic exposure.
Advantages
- Reduced risks of noncompliance
- Minimal systemic exposure
- More efficient drug delivery and treatment
Publications
- Yang, R., Okonkwo, O. S., Zurakowski, D., & Kohane, D. S. (2018). Synergy between chemical permeation enhancers and drug permeation across the tympanic membrane. Journal of controlled release: official journal of the Controlled Release Society, 289, 94–101. https://doi.org/10.1016/j.jconrel.2018.06.019
- Khoo, X., Simons, E. J., Chiang, H. H., Hickey, J. M., Sabharwal, V., Pelton, S. I., Rosowski, J. J., Langer, R., & Kohane, D. S. (2013). Formulations for trans-tympanic antibiotic delivery. Biomaterials, 34(4), 1281–1288. https://doi.org/10.1016/j.biomaterials.2012.10.025
