Encapsulation system
AssigneeLiving Cell Products Pty Ltd.
InventorsAlfred Vasconcellos, Dwaine Emerich, Chris Thanos, Briannan Bintz, Marilyn Sandra Geaney, Stephen John Martin Skinner, Paul Lip Jin Tan
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Abstract
The present invention is directed to a composition comprising high mannuronic acid-containing alginate and a polycation having a polydispersity index of less than 1.5. The composition is particularly useful for making biocompatible microcapsules containing living cells for allo- or xeno-transplantation. Such microcapsules have enhanced durability and can maintain their structural and functional integrity over long periods of time compared to prior art alginate microcapsules.
Claims61
1-82. (canceled)
A composition comprising alginate and a polycation, wherein said polycation has an average molecular weight of 10 to 40 kDa and a polydispersity index of less than about 1.5 and wherein the polycation is not poly-L-lysine, and wherein the alginate has a mannuronic acid concentration selected from the group consisting of (i) between from about 50% to about 95% mannuronic acid residues, (ii) between from about 50% to about 90% mannuronic acid residues;
- (iii) between from about 50% to about 70% mannuronic acid residues, and (iv) between about 80% and about 90%.
A biocompatible microcapsule comprising a core layer of a high mannuronic acid alginate cross-linked with a cationic cross-linking agent, an intermediate layer of polycations forming a semi-permeable membrane, and an outer layer of a high mannuronic acid alginate, wherein the high mannuronic acid alginate in the core and outer layers is the same or different and contains between from about 50% to about 95% mannuronic acid residues, wherein the polycation layer is not comprised of poly-L-lysine.
A method of preparing a biocompatible microcapsule comprising the steps:
- a) dissolving a high mannuronic acid containing alginate in isotonic saline to a concentration of between about 1.0% to 2.0% w/v;
- b) spraying the dissolved alginate solution of step a) through an air- or frequency-based droplet generator into a stirring solution of an excess of a cross-linking agent to form gelled capsules;
- c) coating the gelled capsules of step b) with a polycation having an average molecular weight of 10-40 kDa and a polydispersity index of less than 1.5, wherein the polycation is not poly-L-lysine;
- d) dissolving a high mannuronic acid alginate in isotonic saline to a concentration of about 0.01 to about 1.7% w/v and applying as a final coating to the capsule of step c);
- and
- e) collecting the microcapsules;
- wherein the high mannuronic acid-containing alginate of steps a) and d) is the same or different and contains between about 50% to about 95% mannuronic acid residues.
A method of preparing microencapsulated cells comprising the steps:
- a) incubating living cells in a solution of high mannuronic acid containing alginate dissolved in isotonic saline to a concentration of between about 1.0% and 2.0% w/v;
- b) spraying the cell-containing alginate solution of step c) through an air- or frequency-based droplet generator into a stirring solution of an excess of a cross-linking agent to form gelled cell-containing capsules;
- c) coating the gelled cell-containing capsules of step b) with a polycation having an average molecular weight of 10-40 kDa and a polydispersity index of less than 1.5;
- d) dissolving a high mannuronic acid containing alginate in isotonic saline to a concentration of about 0.01 to about 1.7% w/v and applying as a final coating to the cell-containing capsules of step c);
- and
- e) collecting the cell-containing microcapsules;
- wherein the high mannuronic acid containing alginate of steps a) and d) is the same or different contains from about 50% to about 95% mannuronic acid residues;
- and wherein the polycation is not poly-L-lysine.
A method for coating non-degradable cell delivery construct comprising the steps:
- a) immersing the non-degradable cell delivery construct in a solution of high mannuronic acid containing alginate dissolved in isotonic saline to a concentration of between 1.0% to 2.0% w/v;
- b) incubating the construct of step a) in a solution containing an excess of a cross-linking agent to form a gelled coating;
- c) further coating the gelled construct of step b) with a polycation having an average molecular weight of 10-40 kDa and a polydispersity index of less than 1.5;
- d) dissolving a high mannuronic acid containing alginate in isotonic saline to a concentration of from about 0.01 to about 1.7% w/v and applying as a final coat to produce an immunoisolatory membrane coated non-degradable cell delivery construct;
- and
- e) isolating the immunoisolatory membrane coated non-degradable cell delivery construct;
- wherein the high mannuronic acid containing alginate of steps a) and d) is the same or different and contains between about 50% to about 95% mannuronic acid residues;
- and wherein the polycation is not poly-L-lysine.
Dependencies are inferred from the claim text.