Localized and non-invasive delivery of therapeutics across barriers in the body is challenging. Examples include the flux of drugs across the tympanic membrane (TM) for the treatment of middle ear infections, and across the round window to treat inner ear disease. With the emergence of macromolecular therapies, the question arises as to whether such delivery can be achieved with macromolecules. Here, we have used polyethylene glycols (PEGs) in solutions to investigate macromolecular permeation across the TM in the chinchilla ex vivo. As the molecular weight of PEG increased, flux across the TM decreased, with an exponential relationship between the apparent diffusion coefficient and the molecular weight of the polymers. PEG flux was further decreased if it was released from a poloxamer 407 hydrogel, and lessened with increasing hydrogel concentration. Our results provide a framework for understanding the permeation of macromolecules noninvasively across barriers.
Keywords: Across barriers; Molecular weight; Noninvasive trans-tympanic delivery; Polyethylene glycol.