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High-flow microinfusion: tissue penetration and pharmacodynamics

P F Morrison1, D W Laske, H Bobo

  • 1Biomedical Engineering and Instrumentation Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.

The American Journal of Physiology
|January 1, 1994
PubMed
Summary

High-flow microinfusion enables efficient delivery of macromolecules to large brain volumes. This method offers uniform dosing, reducing toxicity risks compared to traditional methods.

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Area of Science:

  • Neuroscience
  • Biomedical Engineering
  • Pharmacology

Background:

  • Delivering macromolecules to the brain presents challenges due to tissue barriers and the need for precise dosing.
  • Traditional low-flow (diffusive) methods often result in uneven distribution and potential toxicity from concentration gradients.

Purpose of the Study:

  • To evaluate the efficacy of high-flow microinfusion for delivering macromolecules to large brain volumes.
  • To compare the penetration and dosing uniformity of high-flow versus low-flow microinfusion techniques.

Main Methods:

  • Modeling the delivery of approximately 180-kDa macromolecules at a flow rate of 3 microliters/min into homogeneous brain tissue.
  • Predicting concentration profiles and penetration depth over a 12-hour interval.
  • Assessing the penetration advantage of high-flow (convective) over low-flow (diffusive) administration at a fixed pharmacodynamic effect.

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Main Results:

  • High-flow microinfusion can achieve a 1.5-cm radius penetration in 12 hours with a relatively flat concentration profile.
  • This technique provides uniform tissue dosing, mitigating toxicity associated with concentration gradients.
  • Compared to low-flow infusion, high-flow administration demonstrated 5- to 10-fold increases in treatment volume, exceeding 10 cm³ for a macromolecule with a 33.5-hour degradation time.

Conclusions:

  • High-flow microinfusion is an effective method for delivering macromolecules to extensive brain regions within practical timeframes.
  • The technique offers superior volume delivery and uniform dosing compared to low-flow methods, with potential for reduced toxicity.
  • This approach holds promise for the administration of various diagnostic and therapeutic agents, including radioimmunoconjugates, enzymes, and growth factors.