Delivery of small interfering RNA and micro RNA through nanogels containing hydrophobic pseudo-peptides
Nanoscale, pH-responsive polycationic networks useful for the delivery of anionic biologic therapeutics and associated methods.
1. A composition comprising a hydrogel, the hydrogel comprising a plurality of crosslinked copolymers, wherein each copolymer comprises 2-(diethylamino) ethyl methacrylate (DEAEMA), N-methacryloyl L-phenylalanine methyl ester (MAPA), and poly(ethylene glycol) methyl ether methacrylate (PEGMA).
2. The composition of claim 1 , further comprising a plurality of polyoxazoline polymers covalently attached to the hydrogel.
3. The composition of claim 1 , further comprising a plurality of polyoxazoline polymers covalently attached to and at least partially disposed on an exterior surface of the hydrogel.
4. The composition of claim 1 , further comprising an anionic therapeutic agent or a nucleic acid molecule disposed within the hydrogel.
5. The composition of claim 1 , wherein the hydrogel has a positive surface charge at about pH 7.4.
6. The composition of claim 1 , wherein the hydrogel has a collapsed structure at about pH 7.4.
7. The composition of claim 1 , wherein the hydrogel has a z-average particle size diameter of from about 20 nm to about 200 nm.
8. The composition of claim 1 , wherein each copolymer comprises a dimethacrylate crosslinker selected from the group consisting of ethylene glycol dimethacrylate (EGDMA), tetra(ethylene glycol) dimethacrylate (TEGDMA), and poly(ethylene glycol) dimethacrylate (PEGDMA), or combinations thereof.
9. The composition of claim 8 , wherein the dimethacrylate crosslinker comprises tetra(ethylene glycol) dimethacrylate (TEGDMA).
10. A method for treating a gastrointestinal disease in a subject comprising: providing at a pH of less than or equal to about 6.5, a pH responsive polycationic hydrogel, the pH responsive polycationic hydrogel comprising a plurality of crosslinked copolymers, wherein each copolymer comprises 2-(diethylamino) ethyl methacrylate (DEAEMA), N-methacryloyl L-phenylalanine methyl ester (MAPA), and poly(ethylene glycol) methyl ether methacrylate (PEGMA), and wherein the pH responsive polycationic hydrogel comprises an anionic therapeutic or a nucleic acid molecule; and introducing the pH responsive polycationic hydrogel to a disease site in the subject's gastrointestinal tract.
11. The method of claim 10 , wherein the disease site is selected from the group consisting of a gastrointestinal carcinoma, an active site of Crohn's disease, an active site of ulcerative colitis, and an active site of celiac disease.