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Rate-programmed drug delivery systems (DDS) are designed to release drugs at specific, controlled rates to maintain consistent therapeutic levels. These systems are categorized based on their release mechanisms, including dissolution-controlled DDS, diffusion-controlled DDS, and combined dissolution-diffusion-controlled DDS.In dissolution-controlled DDS, the release rate depends on the slow dissolution of the drug itself or the surrounding matrix. Drugs with inherently slow dissolution rates,...

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Modeling iontophoretic drug delivery in a microfluidic device.

Maryam Moarefian1, Rafael V Davalos, Danesh K Tafti

  • 1Department of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.

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Summary

This study introduces an iontophoresis-on-chip platform for precise cancer drug delivery. Optimized electrical fields significantly enhanced carboplatin delivery and triple-negative breast cancer cell death.

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Area of Science:

  • Biomedical Engineering
  • Cancer Therapeutics
  • Drug Delivery Systems

Background:

  • Iontophoresis utilizes electrical fields for targeted drug delivery, showing promise for in vivo cancer treatment.
  • Precise modeling of electric fields in cell cultures is crucial for optimizing iontophoretic drug delivery to tumors.
  • Existing methods lack precise quantification of drug delivery and efficacy in tumor microenvironments.

Purpose of the Study:

  • To develop and validate an iontophoresis-on-chip (IOC) platform for precise quantification of drug delivery and anti-cancer efficacy.
  • To model and optimize low-intensity electric fields for iontophoretic delivery of chemotherapeutics to cancer cells.
  • To investigate the transport of charged drugs through extracellular matrix models using microfluidic devices.

Main Methods:

  • Developed a heparin-based hydrogel microfluidic device to simulate extracellular matrix and MDA-MB-231 triple-negative breast cancer cells.
  • Employed finite element modeling to compute drug concentration based on diffusion and electrophoresis.
  • Validated the IOC platform by comparing predicted fluorescent dye concentrations with actual measurements.

Main Results:

  • A 50 mV DC electric field and 3 mA current significantly enhanced carboplatin delivery.
  • Demonstrated a significant increase in tumor cell death (39.13% ± 12.86) with optimized iontophoresis.
  • Model predictions for drug transport were validated using the IOC platform with fluorescent dye.

Conclusions:

  • The IOC platform and mathematical model offer a promising approach for precise chemotherapeutic drug delivery to solid tumors.
  • Optimized iontophoretic parameters can significantly improve drug delivery efficiency and cancer cell killing.
  • Further development of the IOC platform could incorporate epidermal cell layers for more comprehensive skin modeling.