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A novel system for trigger-controlled drug release from polymer capsules.

David A Fluri1, Christian Kemmer, Marie Daoud-El Baba

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We developed CellEase, a novel system for controlled protein therapeutic release using engineered cells within capsules. This technology enables trigger-controlled discharge of biologics, offering new therapeutic possibilities.

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Area of Science:

  • Biotechnology
  • Materials Science
  • Drug Delivery

Background:

  • Current protein therapeutic delivery methods include continuous or tissue-specific release from implants or engineered extracellular matrices.
  • Trigger-controlled release from synthetic implants is highly desirable for specific therapeutic applications.

Purpose of the Study:

  • To design and characterize a novel two-component system, CellEase, for trigger-controlled release of protein therapeutics.
  • To demonstrate the in vivo efficacy of CellEase for controlled protein discharge.

Main Methods:

  • Developed CellEase: cellulose sulfate (CS)-poly-diallyldimethyl ammonium chloride (pDADMAC) capsules containing mammalian sensor cells engineered for inducible secretion of a modified cellulase (SecCell).
  • Engineered SecCell for doxycycline- or erythromycin-inducible expression and demonstrated its ability to internally rupture CS-pDADMAC capsules.
  • Co-encapsulated sender cells expressing SecCell with producer cell lines expressing therapeutic proteins for controlled release kinetics.

Main Results:

  • SecCell was successfully glycosylated, secreted by mammalian cells, and efficiently ruptured CS-pDADMAC capsules internally.
  • Inducible expression of SecCell enabled time-dependent, trigger-controlled discharge of therapeutic proteins, with kinetics tunable by inducer concentration and cell amount.
  • Demonstrated independent, trigger-induced release of different proteins from separate capsule populations.
  • In vivo studies in mice showed doxycycline-controlled release of a model glycoprotein from implanted capsules into the bloodstream.

Conclusions:

  • CellEase technology provides a versatile platform for trigger-controlled protein therapeutic release.
  • The system allows for independent release of multiple biologics and tunable release kinetics.
  • In vivo validation suggests potential for novel therapeutic applications requiring precise control over biologic delivery.