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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
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Active transmembrane drug transport in microgravity: a validation study using an ABC transporter model.

Sergi Vaquer1, Elisabet Cuyàs2, Arnau Rabadán3

  • 1Departament de Farmacologia Humana, Institut Municipal d'Investigació Mèdica de Barcelona (IMIM), Barcelona, 08003, Spain ; Corporació Sanitària i Universitària Parc Taulí, Sabadell, 08208, Spain.

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Microgravity significantly reduces the transport activity of the MRP2 transporter, impacting drug efficacy and metabolism during spaceflight. This study validates a new method for studying transporter function in microgravity.

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Area of Science:

  • Space biology
  • Cellular physiology
  • Pharmacology

Background:

  • ATP-binding cassette (ABC) transporters are crucial for cellular functions and drug transport.
  • Microgravity affects ABC transporter expression and activity, potentially causing health issues during spaceflight.
  • Existing methods cannot assess transporter functionality in microgravity.

Purpose of the Study:

  • To adapt and validate a Vesicular Transport Assay for studying MRP2 transporter activity in microgravity.
  • To evaluate the impact of microgravity on estradiol-17-β-glucuronide transport by MRP2.
  • To establish a reliable method for assessing transporter function during parabolic flights.

Main Methods:

  • Adapted a Vesicular Transport Assay to measure MRP2-mediated E17βG transport.
  • Conducted experiments during parabolic flights to simulate microgravity.
  • Compared microgravity results with 1g ground controls using identical equipment and protocols.
  • Utilized a high-sensitivity drug detection protocol for sample analysis.

Main Results:

  • The adapted assay demonstrated high accuracy and sensitivity in both microgravity and 1g conditions.
  • On-ground sample transport activity met commercial standards, validating the methodology.
  • MRP2 net transport activity was significantly reduced in microgravity.
  • Simple diffusion signals were also reduced under microgravity conditions.

Conclusions:

  • The developed technology successfully measures transporter activity in microgravity, validating its utility.
  • Microgravity significantly impairs MRP2 transporter function, with potential implications for drug metabolism in space.
  • Further research is needed to elucidate the underlying mechanisms, but the method offers new avenues for space and terrestrial medicine.