Polymeric carriers for delivery of therapeutic agents
View Patent ↗A polymer includes a hydrophobic polymer backbone, a first plurality of pendant groups attached to the hydrophobic polymer backbone and including a first moiety including at least one group selected for ionic interaction with a second therapeutic agent, and a second plurality of pendant groups attached to the hydrophobic polymer backbone and including at least one hydrophilic polymer. The first moiety is attached via a labile bond and is released in vivo from the polymer to provide a biologically or therapeutically active form of a first therapeutic compounds.
1 . A polymer, comprising:
a hydrophobic polymer backbone,
a first plurality of pendant groups attached to the hydrophobic polymer backbone and comprising a moiety attached to the hydrophobic polymer backbone via a bond which is labile in vivo to release a first therapeutic compound which is a COX inhibitor, the moiety comprising a group to ionically interact with a second therapeutic compound, different from the first therapeutic compound, and
a second plurality of pendant groups attached to the hydrophobic polymer backbone and comprising at least one hydrophilic polymer.
2 . The polymer of claim 1 wherein the hydrophobic polymer backbone is formed via radical polymerization of vinyl monomers.
3 . The polymer of claim 2 wherein the hydrophobic polymer backbone is formed via a reversible-deactivation radical polymerization.
4 . The polymer of claim 1 wherein the bond which is labile in vivo includes at least one of a reductive sensitive linkage, a pH-sensitive linkage, a ROS-sensitive linkage, a hypoxia-sensitive linkage, or a protease-sensitive linkage.
5 . The polymer of claim 1 further comprising a third plurality of pendant groups attached to the hydrophobic polymer backbone and comprising at least one targeting group to target a region of interest in vivo.
6 . The polymer of claim 5 wherein the at least one targeting group comprises a folate group, anisamide, peptide, or antibody.
7 . The polymer of claim 5 wherein the at least one targeting group comprises a folate group.
8 . The polymer claim 1 wherein the first therapeutic compound further includes a group capable of interacting via π-π bonding.
9 . The polymer of claim 8 wherein the first therapeutic compound is 5-aminosalicylic acid, acedofenac, diclofenac, mefenamic acid, tolfenamic acid, sulfasalazine, balsalazide, olsalazine, or a derivative thereof which is active as a COX inhibitor.
10 . The polymer of claim 8 wherein the first therapeutic compound is 5-aminosalicylic acid.
11 . The polymer of claim 1 wherein a plurality of the polymers forms a micelle having a diameter less than 100 nm when combined with the second therapeutic compound.
12 . The polymer of claim 1 wherein the second therapeutic compound includes an amino group to ionically interact with the group of the moiety.
13 . The polymer of claim 1 wherein the second therapeutic compound further includes a group to interact via π-π bonding.
14 . The polymer of claim 1 wherein the second therapeutic compound is an anticancer compound, an antiviral compound, an antibiotic compound, an antimycotic compound, an anti-rejection compound, an analgesic compound, an antioxidant compound, an immunomodulating compound, an antifungal compound, or an anti-inflammatory compound.
15 . The polymer of claim 1 wherein the second therapeutic compound is doxorubicin, pirarubicin, aclarubicin, idarubicin, amrubicin, daunorubicin, epirubicin, cisplatin, nedaplatin, oxaliplatin, carboplatin, irinotecan, imatinib, lapatinib, dabrafenib, trametinib, alpelisib, osimertinib, sunitinib, ketoconazole, miconazole, fluconazole, olaparib, rucaparib, niraparib, talazoparib, veliparib, MK-2206 or a peptide.
16 . The polymer of claim 1 wherein the first moiety is attached to the hydrophobic polymer backbone via a linker which interacts with the second therapeutic compound.
17 . A formulation, comprising: a plurality of polymers comprising a hydrophobic polymer backbone, a first plurality of pendant groups attached to the hydrophobic polymer backbone and comprising a moiety attached to the hydrophobic polymer backbone via a bond which is labile in vivo to release as a first therapeutic compound which is a COX inhibitor and a second plurality of pendant groups attached to the hydrophobic polymer backbone and comprising at least one hydrophilic polymer and a second therapeutic compound, different from the first therapeutic compound, the moiety comprising a group to ionically interact with a group of the second therapeutic compound.
18 . The formulation of claim 17 wherein each of the first therapeutic compound and the second therapeutic compound is a small molecule compound.
19 . The formulation of claim 18 wherein each of the first therapeutic compound and the second therapeutic compound has a molecular weight below 1.5 kDa or 1 kDa.
20 . The formulation of claim 17 wherein the hydrophobic polymer backbone is formed via radical polymerization of vinyl monomers.
21 . The formulation of claim 20 wherein the hydrophobic polymer backbone is formed via a reversible-deactivation radical polymerization.
22 . The formulation of claim 17 wherein the bond which is labile in vivo includes at least one of a reductive sensitive linkage, a pH-sensitive linkage, a ROS-sensitive linkage, a hypoxia-sensitive linkage, or a protease-sensitive linkage.
23 . The formulation of claim 17 wherein the polymer further comprises a third plurality of pendant groups attached to the hydrophobic polymer backbone and comprising at least one targeting group to target a region of interest in vivo.
24 . The formulation of claim 23 wherein the at least one targeting group comprises a folate group, anisamide, peptide, or antibody.
25 . The formulation of claim 23 wherein the at least one targeting group comprises a folate group.