Pharmaceutical Research

, Volume 23, Issue 3, pp 557–564 | Cite as

Magnetically Responsive Polymeric Microparticles for Oral Delivery of Protein Drugs

  • Jianjun Cheng
  • Benjamin A. Teply
  • Seok Yoon Jeong
  • Christopher H. Yim
  • Dennis Ho
  • Ines Sherifi
  • Sangyong Jon
  • Omid C. Farokhzad
  • Ali Khademhosseini
  • Robert S. Langer
Research Paper

Purpose

Protein drugs cannot be delivered efficiently through oral routes. To address this challenge, we evaluated the effect of prolonged gastrointestinal transit on the bioavailability of insulin carried by magnetically responsive microparticles in the presence of an external magnetic field.

Methods

Magnetite nanocrystals and insulin were coencapsulated into poly(lactide-co-glycolide) (PLGA) microparticles and their effects on hypoglycemia were evaluated in mice in the presence of a circumferentially applied external magnetic field.

Results

A single administration of 100 U/kg of insulin–magnetite–PLGA microparticles to fasted mice resulted in a reduction of blood glucose levels of up to 43.8% in the presence of an external magnetic field for 20 h (bioavailability = 2.77 ± 0.46 and 0.87 ± 0.29% based on glucose and ELISA assay, respectively), significantly higher than similarly dosed mice without a magnetic field (bioavailability = 0.66 ± 0.56 and 0.30 ± 0.06%, based on glucose and ELISA assay, respectively).

Conclusions

A substantially improved hypoglycemic effect was observed in mice that were orally administered with insulin–magnetite–PLGA microparticles in the presence of an external magnetic field, suggesting that magnetic force can be used to improve the efficiency of orally delivered protein therapeutics.

Key Words

insulin magnetic particles microparticles oral delivery protein drugs 

Notes

Acknowledgments

The authors would like to thank Dr. George Kodokian, Dr. Hongming Chen, Dr. Daniel Kohane, Dr. Jeffrey Karp, and Dr. Yoon Yeo for their helpful discussions. This research was supported by the DuPont–MIT Alliance and the NIH. Ines Sherifi was financially supported by the University of Toronto.

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Jianjun Cheng
    • 1
  • Benjamin A. Teply
    • 1
    • 2
  • Seok Yoon Jeong
    • 1
  • Christopher H. Yim
    • 1
  • Dennis Ho
    • 3
  • Ines Sherifi
    • 1
    • 2
  • Sangyong Jon
    • 4
  • Omid C. Farokhzad
    • 2
    • 5
  • Ali Khademhosseini
    • 5
    • 6
  • Robert S. Langer
    • 1
    • 5
  1. 1.Department of Chemical EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Department of AnesthesiologyBrigham and Women's Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Department of BiologyMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Department of Life ScienceGwangju Institute of Science and TechnologyGwangjuSouth Korea
  5. 5.Division of Health Sciences and TechnologyMassachusetts Institute of TechnologyCambridgeUSA
  6. 6.Department of MedicineBrigham and Women's Hospital, Harvard Medical SchoolBostonUSA

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