Permeation of polyethylene glycols across the tympanic membrane
Wei Zhang,
Brendan Harty,
Yueqin Zheng,
Zipei Zhang,
Xiyu Li,
Dali Wang,
Daniel S. Kohane
Affiliations
Wei Zhang
Laboratory for Biomaterials and Drug Delivery, The Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
Brendan Harty
Laboratory for Biomaterials and Drug Delivery, The Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
Yueqin Zheng
Laboratory for Biomaterials and Drug Delivery, The Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
Zipei Zhang
Laboratory for Biomaterials and Drug Delivery, The Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
Xiyu Li
Laboratory for Biomaterials and Drug Delivery, The Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
Dali Wang
Laboratory for Biomaterials and Drug Delivery, The Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
Daniel S. Kohane
Corresponding author.; Laboratory for Biomaterials and Drug Delivery, The Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
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.
