Journal Club: Demonstration of osmotic pump implantation methodology for chronic drug delivery in mouse model.

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Today's journal article

Depreux F, Whitlon D, Richter CP. ALZET pump implantation in mice for chronic drug delivery to the cochlea. 

Why I picked this article

This paper outlines a surgical technique to implant ALZET mini-osmotic pumps that can release drugs into the mouse cochlea over a prolonged period, a potentially powerful tool for chronic intervention studies.

Drug delivery to the inner ear organ for hearing, the cochlea, is a challenge. The intratympanic injection of the drug is a local drug-delivery method, where the drug is injected into the middle ear and subsequently (presumably) diffuses into the cochlea. The contact time for the drug to diffuse into the cochlea is limited with the standard intratympanic injection, and hence several approaches to improve the intratympanic drug administration methodology have been developed, including a more viscous hydrogel, which can remain in the middle ear for longer, or the development of a drug-containing sponge. These methodologies are still short and single-dose administration. 

In this publication, researchers have developed an implant which will continuously deliver a drug for a much longer period of time. 

Some of the research findings

Drug delivery device - the osmotic pump:

  • ALZET micro-osmotic pumps (Model 1004, Durect Corporation, Cupertino, CA) 
  • Delivers fluids over four weeks at a 0.11 μL/hour flow rate
  • The catheter was custom-designed to have a tip diameter of 130μm
  • The tip of the catheter was aimed at the inside of the cochlea. 

Animal model:

  • Ten-week-old CBA/CaJ male mice were used.
  • From the ventral aspect (throat side), a cut was made between the muscles to access the otic bullae. 
  • The otic bullae, containing the middle ear, were opened to expose the cochlea. 
  • A hole was made on the cochlea, through which the tip of the catheter was inserted. The catheter was angled toward the cochlear apex (the tip of the spiral). 
Figure 3 d. The catheter tip inserted through the hole into the cochlea. Depreux et al. 2025.

Finding post-surgery:

  • Complications from/during the surgery included bleeding and changes in breathing rate, but did not affect their recovery time. 
  • 19 out of 45 mice developed vestibular symptoms up to 72 hours post-surgery. 

Haruna's takeaway

Overall, this research illustrated the surgical procedure of implanting this drug-eluting osmotic pump. While the pump seems to be a commercially available model made for use in the brain, researchers show the steps necessary to make the tip size smaller to allow its use for the cochlea. Sharing of methods like this is always helpful for the research fields and appreciated. I wonder what the impact of an increase in fluid volume is as the osmotic pump administers a small, but defined volume of fluid. It must slightly elevate the pressure in the cochlea by increasing the fluid volume.  

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This is Haruna's 43/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.