Hyper comb-branched polymer conjugates
AssigneesDendritech, Inc., University of Michigan
InventorsRui Yin, Donald A. Tomalia, David M. Hedstrand, Douglas R. Swanson, James R. Baker, Jr., Jolanta F. Kukowska-Latallo
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Abstract
A novel class of hyper comb-branched polymers conjugated with carried materials are disclosed.
Claims92
A hyper comb-branched polymer conjugate of the formula:
- H.sub.v --M.sub.b
- wherein H is a hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;
- M is a carried material;
- v is an integer of at least 1;
- and
- b is an integer of at least 1.
A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains, wherein said hyper comb-branched polymer has a grafting density of from about 0.1% to about 90%.
A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains, wherein said hyper comb-branched polymer has an interior void volume of from about 10 angstroms to about 500 angstroms.
A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains wherein said hyper comb-branched polymer comprises alternating regions of (i) a first region having a grafting density of less than about 50%, and (ii) a second region having a grafting density of more than about 50%.
A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains, wherein said hyper comb-branch polymer has at least one chemical moiety disposed about the periphery of said polymer, said moiety selected from the group consisting of --NH.sub.2, --COOH, --COOMe, --NH.sub.4, --PEOX, --PEG, --PEO, and combinations thereof.
A hyper comb-branched polymer conjugate of the formula:
- H.sub.v --M.sub.b --T.sub.z
- wherein H is a hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;
- M is a carried material;
- T is a target director;
- v is an integer of at least 1;
- b is an integer of at least 1;
- and
- z is an integer of at least 1.
A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material wherein said hyper comb-branched polymer has a maximum diameter of about 100 nm, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains.
A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains, wherein said hyper comb-branched polymer has a hydrophobically-modified region, said region being at least one of an interior region or an exterior region.
A hyper comb-branched polymer conjugate comprising a hyper comb-branched polymer and a carried material, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains, wherein said hyper comb-branched polymer has a hydrophilically-modified region, said region being at least one of an interior region or an exterior region.
A hyper comb-branched polymer conjugate of the formula:
- H.sub.v --M.sub.b --M'.sub.a
- wherein H is a hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;
- M is a first carried material;
- M' is a second carried material different than said first carried material;
- v is an integer of at least 1;
- b is an integer of at least 1;
- and
- a is an integer of at least 1.
A composition comprising a hyper comb-branched polymer conjugate of the formula:
- H.sub.v --M.sub.b
- wherein H is a hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;
- M is a first carried material;
- v is an integer of at least 1;
- and
- b is an integer of at least 1.
A method of carrying genetic material, said method comprising:
- providing a hyper comb-branched polymer having a plurality of positively charged sites, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;
- and
- conjugating said polymer with genetic material having a plurality of negatively charged sites.
A process for preparing a complex of hyper comb-branched polymer and genetic material comprising:
- reacting said hyper comb-branched polymer with said genetic material in a solvent at a temperature which facilitates the complexing of said genetic material with said hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to the zero generation linear oligomeric branch chains.
The process of clam 62 wherein said hyper comb-branched polymer has a predominantly cationic surface, said process comprising electrostatically attaching genetic material to said polymer to create said complex.
A process for forming a genetic material:
- hyper comb-branched polymer complex comprising:
- mixing, in water, sufficient genetic material to yield a final concentration from about 1 to about 10 .mu.g per mL, with sufficient hyper comb-branched polymer, having positive surface functionality, to yield a genetic material:
- polymer charge ratio from about 1:10 to about 1:10,000, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;
- said mixing being done at a pH of about 5 to about 10 and at a temperature from about 20 to about 40.degree. C.
A composition comprising a hyper comb-branched polymer conjugate of the formula:
- H.sub.v --M.sub.b --T.sub.z
- wherein H is a hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;
- M is a carried material;
- T is a target director;
- v is an integer of at least 1;
- b is an integer of at least 1;
- and
- z is an integer of at least 1.
A composition comprising a hyper comb-branched polymer conjugate of the formula:
- H.sub.v --M.sub.b --M'.sub.a
- wherein H is a hyper comb-branched polymer, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;
- M is a first carried material;
- M' is a second carried material different than said first carried material;
- v is an integer of at least 1;
- b is an integer of at least 1;
- and
- a is an integer of at least 1.
A process for forming a concentrated genetic material:
- hyper comb-branched polymer complex which can be diluted for use comprising:
- mixing, in water, sufficient genetic material to yield a concentration from about 1 to about 10 .mu.g per 20 .mu.L, with sufficient hyper comb-branched polymer, having positive surface functionality, to yield a genetic material:
- polymer charge ratio from about 1:10 to about 1:10,000, said hyper comb-branched polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;
- said mixing being done at a pH from about 5 to about 10 and at a temperature from about 20 to about 40.degree. C.
A method of effecting cell transfection and bioavailability of genetic material comprising providing a complex of a hyper comb-branched polymer and genetic material, and making said complex available to cells to be transfected, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains.
A method for transporting genetic material through a cellular membrane and into a cellular nucleus comprising:
- complexing said genetic material with hyper comb-branched polymer, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains;
- followed by making said complex available to cells to be transfected.
A method for protecting genetic material from digestion during transit to and transfection into a cell comprising:
- complexing said genetic material with hyper comb-branched polymer prior to exposing said genetic material to digestive enzymes, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains.
A method for stabilizing and compacting genetic material comprising complexing said genetic material with hyper comb-branched polymer, said hyper comb-branch polymer including at least a core, a plurality of zero generation linear oligomeric branch chains grafted to the core, and a plurality of first generation linear oligomeric branch chains grafted to zero generation linear oligomeric branch chains.
Dependencies are inferred from the claim text.