Microcapsules and composite microreactors for immunoisolation of

Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Animal or plant cell

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424423, 435177, 435178, 435182, 435382, 435395, 435397, A61K 3512, C12N 1110, C12N 1104, C12N 500

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active

061269360

ABSTRACT:
Microcapsules and composite microreactors are prepared that immunoisolate living cells such as islet cells or genetically engineered cells. A reduced volume microcapsule is formed by coating a gel matrix particle with a polyamino acid of 15,000 daltons or less molecular weight to reduce volume of the particle by at least 30% as compared to volume prior to coating. A composite microreactor includes the microcapsule containing cell embedded in a gel matrix and provides a molecular weight cutoff that prevents molecules larger than about 400,000 daltons from containing the living cell. A double composite microreactor includes an internal particle that includes an internal particle gel matrix containing a living cell and having a coating, a particle that includes the internal particle embedded in a particle gel matrix and a coating, and a gel super matrix in which the particle is embedded. At least one of the coatings is a volume reducing coating of polyamino acid of 15,000 daltons or less molecular weight. The gel matrices may be alginate, the polyamino acid may be polylysine or polyornithine, and at least one of the gel matrices or coatings may be treated by aging for between 2 hours and 14 days. The internal particle, particle and composite microreactor may have diameters respectively between 50 and 700 microns, 400 and 800 microns and 300 and 1500 microns. to be implanted so there is little or no need for immunosuppressant or antifibrotic drugs. A reduced volume microcapsule is formed by coating a gel matrix particle with a polyamino acid of 15,000 daltons or less molecular weight to reduce volume of the particle by at least 30% as compared to volume prior to coating. A composite microreactor is provided by embedding the microcapsule when containing a living cell in a gel matrix to obtain a molecular weight cutoff that prevents molecules larger than about 400,000 daltons from contacting the living cell. A double composite microreactor is formed containing an internal particle including an internal particle gel matrix containing a living cell and having a coating, a particle including the internal particle embedded in a particle gel matrix having a coating, and a gel super matrix in which the particle is embedded. At least one of the coatings is a volume reducing coating of polyamino acid of 15,000 daltons or less molecular weight. The gel matrices may be alginate, the polyamino acid may be polylysine or polyornithine, and at least one of the gel matrices or coatings may be treated by aging for between 2 hours and 14 days. The internal particle, particle and composite microreactor may have diameters respectively between 50 and 700 microns, 400 and 800 microns and 300 and 1500 microns.

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