The use of charge-coupled polymeric microparticles and micromagnets for modulating the bioavailability of orally delivered macromolecules

Benjamin A. Teply, Rong Tong, Seok Y. Jeong, Gaurav Luther, Ines Sherifi, Christopher H. Yim, Ali Khademhosseini, Omid C. Farokhzad, Robert S. Langer, Jianjun Cheng

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Protein drugs have low bioavailability after oral administration, which is due in part to fast transit of the drugs or drug delivery vehicles through the gastrointestinal tract. Increasing the time that the drugs spend in the intestine after dosing would allow for greater absorption and increased bioavailability. We developed a formulation strategy that can be used to prolong intestinal retention of drug delivery vehicles without substantial alterations to current polymeric encapsulation strategies. A model drug, insulin, was encapsulated in negatively charged poly(lactic-co-glycolic acid) (PLGA) microparticles, and the microparticles were subsequently mixed with positively charged micromagnets, whose size will prevent them from being absorbed. Stable complexes formed through electrostatic interaction. The complexes were effectively immobilized in vitro in a model of the mouse small intestine by application of an external magnetic field. Mice that were gavaged with radio-labeled complexes and fitted with a magnetic belt retained 32.5% of the 125I-insulin in the small intestine compared with 5.4% for the control group 6 h after administration (p = 0.005). Furthermore, mice similarly gavaged with complexes encapsulating insulin (120 Units/kg) exhibited long-term glucose reduction in the groups with magnetic belts. The corresponding bioavailability of insulin was 5.11% compared with 0.87% for the control group (p = 0.007).

Original languageEnglish (US)
Pages (from-to)1216-1223
Number of pages8
JournalBiomaterials
Volume29
Issue number9
DOIs
StatePublished - Mar 2008
Externally publishedYes

Keywords

  • Drug delivery
  • Drug release
  • Magnetism
  • Microsphere
  • Protein

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Teply, B. A., Tong, R., Jeong, S. Y., Luther, G., Sherifi, I., Yim, C. H., Khademhosseini, A., Farokhzad, O. C., Langer, R. S., & Cheng, J. (2008). The use of charge-coupled polymeric microparticles and micromagnets for modulating the bioavailability of orally delivered macromolecules. Biomaterials, 29(9), 1216-1223. https://doi.org/10.1016/j.biomaterials.2007.11.018