Polymeric delivery systems
A polymeric delivery system delivers a biologic to cells. In some embodiments, the polymeric delivery system includes polyplexes. Each polyplex includes at least one charged polymer and at least one biologic. The at least one charged polymer includes a polyester copolymer of a polyol and a polycarboxylic acid modified with at least one charged moiety having an opposite charge from a net charge of the at least one biologic. In other embodiments, the polymeric delivery system includes self-assembled particles including a block copolymer and a biologic associated with the block copolymer. The block copolymer includes a first block of a polyester copolymer of a polyol and a polycarboxylic acid and a second block of a second monomer or a second polymer.
1 . A polymeric delivery system comprising self-assembled particles in an aqueous solvent, the self-assembled particles comprising a block copolymer and a biologic associated with the block copolymer, wherein the block copolymer comprises a first block of a polyester copolymer of alternating monomers of a polyol monomer and a polycarboxylic acid monomer and a second block of a hydrophilic monomer or a hydrophilic polymer, wherein the second block is more hydrophilic than the first block and wherein the self-assembled particles are selected from the group consisting of polymersomes, polymeric micelles, and polyplexes; and
wherein the first block has a chemical structure of formula (1):
—[—CO—(CH 2 ) m —R—(CH 2 ) n —CO 2 —CH 2 —CH(OR′)—CH 2 —O—] x (1)
wherein m and n are an integer from 1 to 30; x is an integer from 1 to 75; R is selected from the group consisting of —CH 2 —, —NH—, —NCH 3 —, —O—, —S—S—, —CH═CH—, —C≡C—, —CO 2 —, and —CONH—; and R′ is hydrogen or another replaceable pendant group.
2 . The polymeric delivery system of claim 1 , wherein the self-assembled particles have a number-weighted average particle size in the range of about 10 nm to about 1000 nm.
3 . The polymeric delivery system of claim 1 , wherein the first block is unbranched.
4 . The polymeric delivery system of claim 1 , wherein an alcohol of at least one polyol of the first block is modified to an ester to include an alkyl tail of a least five carbons in length.
5 . The polymeric delivery system of claim 1 , wherein the self-assembled particles are polymersomes.
6 . The polymeric delivery system of claim 1 , wherein the self-assembled particles are polymeric micelles.
7 . The polymeric delivery system of claim 1 , wherein the self-assembled particles are polyplexes.
8 . The polymeric delivery system of claim 1 , wherein the block copolymer and the biologic are associated by ligand interaction or complex coordination.
9 . The polymeric delivery system of claim 1 , wherein the block copolymer is cationic and the biologic is anionic.
10 . The polymeric delivery system of claim 1 , wherein the biologic is selected from the group consisting of a nucleic acid, an amino acid, a peptide, a protein, a gene editing system, an antibody, and a cytokine.
11 . The polymeric delivery system of claim 10 , wherein the biologic comprises a nucleic acid.
12 . A process of forming a polymeric delivery system, the process comprising forming self-assembled particles comprising a block copolymer and a biologic associated with the block copolymer in an aqueous solvent, wherein the block copolymer comprises a first block of a polyester copolymer of alternating monomers of a polyol monomer and a polycarboxylic acid monomer and a second block of a hydrophilic monomer or a hydrophilic polymer, wherein the second block is more hydrophilic than the first block and wherein the self-assembled particles are selected from the group consisting of polymersomes, polymeric micelles, and polyplexes; and
wherein the first block has a chemical structure of formula (1):
—[—CO—(CH 2 ) m —R—(CH 2 ) n —CO 2 —CH 2 —CH(OR′)—CH 2 —O—] x (1)
wherein m and n are an integer from 1 to 30; x is an integer from 1 to 75; R is selected from the group consisting of —CH 2 —, —NH—, —NCH 3 —, —O—, —S—S—, —CH═CH—, —C≡C—, —CO 2 —, and —CONH—; and R′ is hydrogen or another replaceable pendant group.
13 . The process of claim 12 , wherein the self-assembled particles have a number-weighted average particle size in the range of about 10 nm to about 1000 nm.
14 . The process of claim 12 , wherein the self-assembled particles are polymersomes.
15 . The process of claim 12 , wherein the self-assembled particles are polymeric micelles.
16 . The process of claim 12 , wherein the self-assembled particles are polyplexes.
17 . The process of claim 12 , wherein the biologic is selected from the group consisting of a nucleic acid, an amino acid, a peptide, a protein, a gene editing system, an antibody, and a cytokine.
18 . A process of delivering a biologic to cells, the process comprising administering self-assembled particles in an aqueous solvent, the self-assembled particles comprising a block copolymer and the biologic associated with the block copolymer, wherein the block copolymer comprises a first block of a polyester copolymer of alternating monomers of a polyol monomer and a polycarboxylic acid monomer and a second block of a hydrophilic monomer or a hydrophilic polymer, wherein the second block is more hydrophilic than the first block and wherein the self-assembled particles are selected from the group consisting of polymersomes, micelles, and polyplexes; and
wherein the first block has a chemical structure of formula (1):
—[—CO—(CH 2 ) m —R—(CH 2 ) n —CO 2 —CH 2 —CH(OR′)—CH 2 —O—] x (1)
wherein m and n are an integer from 1 to 30; x is an integer from 1 to 75; R is selected from the group consisting of —CH 2 —, —NH—, —NCH 3 —, —O—, —S—S—, —CH═CH—, —C≡C—, —CO 2 —, and —CONH—; and R′ is hydrogen or another replaceable pendant group.
19 . The process of claim 18 , wherein the administering comprises parenterally administering.
20 . The process of claim 18 , wherein the administering comprises administering to the cells ex vivo.
21 . The process of claim 18 , wherein the administering comprises administering to the cells in vitro.
22 . The process of claim 18 , wherein the administering comprises administering to the cells in vivo.
23 . The process of claim 18 further comprising combining the block copolymer and the biologic to form the self-assembled particles.
24 . The process of claim 18 , wherein the self-assembled particles are polymersomes.
25 . The process of claim 18 , wherein the self-assembled particles are polymeric micelles.
26 . The process of claim 18 , wherein the self-assembled particles are polyplexes.
27 . The process of claim 18 , wherein the biologic is selected from the group consisting of a nucleic acid, an amino acid, a peptide, a protein, a gene editing system, an antibody, and a cytokine.
28 . The process of claim 12 , wherein the forming self-assembled particles comprises mixing the block copolymer and the biologic in the aqueous solvent.
29 . The polymeric delivery system of claim 1 , wherein x is an integer from 5 to 75.