Small molecule delivery across a perforated artificial membrane by thermoreversible hydrogel poloxamer 407.

Journal Article (Journal Article)

Microperforations in the round window membrane have been suggested for enhancing the rate and reliability of drug delivery into the cochlea. Intratympanic injection, the most common delivery method, involves injecting therapy into the middle ear to establish a reservoir from which drug diffuses across the round window membrane into the cochlea. This process is highly variable because (i) the reservoir, if liquid, can lose contact with the membrane and (ii) diffusion across the membrane is intrinsically variable even with a stable reservoir. To address these respective sources of variability, we compared the thermoreversible hydrogel poloxamer 407 (P407) to saline as a drug carrier and studied the effect of membrane microperforations on drug diffusion rate. We used Rhodamine B as a drug proxy to measure permeance across an artificial membrane in a horizontal diffusion cell. We found that permeance of Rhodamine B from a saline reservoir was an order of magnitude higher than that from a P407 reservoir across unperforated membranes. Moreover, permeance increased with total perforation cross-sectional area regardless of number of perforations (p < 0.05 for all saline-based experiments), but the same association was not found with P407. Rather, for a P407 reservoir, only a large perforation increased permeance (p < 0.001), while multiple small perforations did not (p = 0.749). These results confirm that for drug dissolved in saline, multiple small perforations can effectively enhance diffusion. However, for drug dissolved in P407, larger perforations are necessary.

Full Text

Duke Authors

Cited Authors

  • Santimetaneedol, A; Wang, Z; Arteaga, DN; Aksit, A; Prevoteau, C; Yu, M; Chiang, H; Fafalis, D; Lalwani, AK; Kysar, JW

Published Date

  • October 2019

Published In

Volume / Issue

  • 182 /

Start / End Page

  • 110300 -

PubMed ID

  • 31326623

Pubmed Central ID

  • PMC6755035

Electronic International Standard Serial Number (EISSN)

  • 1873-4367

International Standard Serial Number (ISSN)

  • 0927-7765

Digital Object Identifier (DOI)

  • 10.1016/j.colsurfb.2019.06.030


  • eng