Multiblock biodegradable hydrogels for drug delivery and tissue treatment
AssigneeFocal, Inc.
InventorsChandrashekhar P. Pathak, Shikha P. Barman, C. Michael Philbrook, Amarpreet S. Sawhney, Arthur J. Coury, Luis Z. Avila, Mark T. Kieras
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Abstract
Gel-forming macromers including at least four polymeric blocks, at least two of which are hydrophobic and at least one of which is hydrophilic, and including a crosslinkable group are provided. The macromers can be covalently crosslinked to form a gel on a tissue surface in vivo. The gels formed from the macromers have a combination of properties including thermosensitivity and lipophilicity, and are useful in a variety of medical applications including drug delivery and tissue coating.
Claims28
A macromer which is capable of forming a gel, the macromer comprising a total of five or ten covalently linked polymeric blocks, wherein:
- a) at least one polymer block is hydrophilic and each hydrophilic polymer block individually has a water solubility of at least 1 gram/liter;
- b) at least two blocks are sufficiently hydrophobic to cause the macromer to aggregate to form micelles in an aqueous continuous phase;
- c) the macromer comprises at least one crosslinkable group;
- d) the macromer comprises at least one thermally sensitive region;
- and
- e) a solution of the macromer is capable of gelling or crosslinking to produce a hydrogel with a temperature dependent volume.
A macromer which is capable of forming a gel, the macromer comprising at least four covalently linked polymeric blocks, wherein:
- a) at least one polymer block is hydrophilic and each hydrophilic polymer block individually has a water solubility of at least 1 gram/liter:
- b) at least two blocks are sufficiently hydrophobic to cause the macromer to aggegate to form micelles in an aqueous continuous phase;
- c) the macromer comprises at least one crosslinkable group;
- d) the macromer comprises at least one thermally sensitive region;
- e) a solution of the macromer is capable of gelling or crosslinking to produce a hydrogel with a temperature dependent volume;
- and
- f) at least one hydrophobic block is separated from any crosslinkable group by at least one hydrophilic block.
A macromer which is capable of forming a gel, the macromer comprising at least four covalently linked polymeric blocks, wherein:
- a) at least one polymer block is hydrophilic and each hydrophilic polymer block individually has a water solubility of at least 1 gram/liter;
- b) at least two blocks are sufficiently hydrophobic to cause the macromer to aggregate to form micelles in an aqueous continuous phase;
- c) the macromer comprises at least one crosslinkable group;
- d) the macromer comprises at least one thermally sensitive region;
- e) a solution of the macromer is capable of gelling or crosslinking to produce a hydrogel with a temperature dependent volume;
- and
- f) the macromer comprises at least two chemically distinct hydrophobic blocks.
A macromer which is capable of forming a gel, the macromer comprising at least four covalently linked polymeric blocks, wherein:
- a) at least one polymer block is hydrophilic and each hydrophlilc polymer block individually has a water solubility of at least 1 gram/liter;
- b) at least two blocks are sufficiently hydrophobic to cause the macromer to aggregate to form micelles in an aqueous continuous phase;
- c) the macromer comprises at least one crosslinkable group;
- d) the macromer comprises at least one thermally sensitive region;
- e) a solution of the macromer is capable of gelling or crosslinking to produce a hydrogel with a temperature dependent volume;
- and
- f) the thermally sensitive region comprises a poloxamer backbone extended with oligolactate moities, wherein the poloxamer-lactate copolymer is terminated by acrylate moieties.
A macromer which is capable of forming a gel, the macromer comprising at least four covalently linked polymeric blocks, wherein:
- a) at least one polymer block is hydrophilic and each hydrophilic polymer block individually has a water solubility of at least 1 gram/liter;
- b) at least two blocks are sufficiently hydrophobic to cause the macromer to aggregate to form micelles in an aqueous continuous phase;
- c) the macromer comprises at least one crosslinkable group;
- d) the macromer comprises at least one thermally sensitive region;
- e) a solution of the macromer is capable of gelling or crosslinking to produce a hydrogel with a temperature dependent volume;
- and
- f) the thermally sensitive region comprises an acrylate capped polyglycolide derivatized poloxamer of about 30% polypropylene oxide content.
Dependencies are inferred from the claim text.